
Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review)
- Authors:
- Yunlong Sun
- Kaifang Wei
- Xudong Liao
- Jian'an Wang
- Li'na Gao
- Bo Pang
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Affiliations: College of Pharmacy, Jining Medical University, Rizhao, Shandong 276826, P.R. China, Gao Shixian National Famous Chinese Medicine Expert Inheritance Studio, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China - Published online on: July 8, 2025 https://doi.org/10.3892/ijmm.2025.5580
- Article Number: 139
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Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
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Lamptey RNL, Chaulagain B, Trivedi R, Gothwal A, Layek B and Singh J: A Review of the common neurodegenerative disorders: Current therapeutic approaches and the potential role of nanotherapeutics. Int J Mol Sci. 23:18512022. View Article : Google Scholar : PubMed/NCBI | |
Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL and Bohr VA: Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol. 15:565–581. 2019. View Article : Google Scholar | |
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, Cummings J and van der Flier WM: Alzheimer's disease. Lancet. 397:1577–1590. 2021. View Article : Google Scholar | |
Kalia LV and Lang AE: Parkinson's disease. Lancet. 386:896–912. 2015. View Article : Google Scholar : PubMed/NCBI | |
Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ and Sobue G: Amyotrophic lateral sclerosis. Lancet. 400:1363–1380. 2022. View Article : Google Scholar : PubMed/NCBI | |
Vaquer-Alicea J and Diamond MI: Propagation of protein aggregation in neurodegenerative diseases. Annu Rev Biochem. 88:785–810. 2019. View Article : Google Scholar | |
Dugger BN and Dickson DW: Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol. 9:a0280352017. View Article : Google Scholar : PubMed/NCBI | |
Gao C, Jiang J, Tan Y and Chen S: Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets. Signal Transduct Target Ther. 8:3592023. View Article : Google Scholar : | |
Kent SA and Miron VE: Microglia regulation of central nervous system myelin health and regeneration. Nat Rev Immunol. 24:49–63. 2024. View Article : Google Scholar | |
Voet S, Srinivasan S, Lamkanfi M and van Loo G: Inflammasomes in neuroinflammatory and neurodegenerative diseases. EMBO Mol Med. 11:e102482019. View Article : Google Scholar : PubMed/NCBI | |
Sun N, Victor MB, Park YP, Xiong X, Scannail AN, Leary N, Prosper S, Viswanathan S, Luna X, Boix CA, et al: Human microglial state dynamics in Alzheimer's disease progression. Cell. 186:4386–4403.e29. 2023. View Article : Google Scholar : PubMed/NCBI | |
Yu H, Chang Q, Sun T, He X, Wen L, An J, Feng J and Zhao Y: Metabolic reprogramming and polarization of microglia in Parkinson's disease: Role of inflammasome and iron. Ageing Res Rev. 90:1020322023. View Article : Google Scholar : PubMed/NCBI | |
Clarke BE and Patani R: The microglial component of amyotrophic lateral sclerosis. Brain. 143:3526–3539. 2020. View Article : Google Scholar | |
Billingham LK, Stoolman JS, Vasan K, Rodriguez AE, Poor TA, Szibor M, Jacobs HT, Reczek CR, Rashidi A, Zhang P, et al: Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation. Nat Immunol. 23:692–704. 2022. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, Gilfillan S, Krishnan GM, Sudhakar S, Zinselmeyer BH, et al: TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell. 160:1061–1071. 2015. View Article : Google Scholar : | |
Zheng Z, Chen M, Feng S, Zhao H, Qu T, Zhao X, Ruan Q, Li L and Guo J: VDR and deubiquitination control neuronal oxidative stress and microglial inflammation in Parkinson's disease. Cell Death Discov. 10:1502024. View Article : Google Scholar | |
Yoon H, Shaw JL, Haigis MC and Greka A: Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity. Mol Cell. 81:3708–3730. 2021. View Article : Google Scholar : PubMed/NCBI | |
Shang C, Su Y, Ma J, Li Z, Wang P, Ma H, Song J and Zhang Z: Huanshaodan regulates microglial glucose metabolism reprogramming to alleviate neuroinflammation in AD mice through mTOR/HIF-1α signaling pathway. Front Pharmacol. 15:14345682024. View Article : Google Scholar | |
Baik SH, Kang S, Lee W, Choi H, Chung S, Kim JI and Mook-Jung I: A breakdown in metabolic reprogramming causes microglia dysfunction in Alzheimer's disease. Cell Metab. 30:493–507.e6. 2019. View Article : Google Scholar : PubMed/NCBI | |
Nugent AA, Lin K, van Lengerich B, Lianoglou S, Przybyla L, Davis SS, Llapashtica C, Wang J, Kim DJ, Xia D, et al: TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge. Neuron. 105:837–854.e9. 2020. View Article : Google Scholar : PubMed/NCBI | |
Chausse B, Kakimoto PA and Kann O: Microglia and lipids: How metabolism controls brain innate immunity. Semin Cell Dev Biol. 112:137–144. 2021. View Article : Google Scholar | |
Lull ME and Block ML: Microglial activation and chronic neurodegeneration. Neurotherapeutics. 7:354–365. 2010. View Article : Google Scholar | |
Fernando KKM and Wijayasinghe YS: Sirtuins as potential therapeutic targets for mitigating neuroinflammation associated with Alzheimer's disease. Front Cell Neurosci. 15:7466312021. View Article : Google Scholar | |
Licata L, Viale G, Giuliano M, Cur igliano G, Chavez-MacGregor M, Foldi J, Oke O, Collins J, Del Mastro L, Puglisi F, et al: Oncotype DX results increase concordance in adjuvant chemotherapy recommendations for early-stage breast cancer. NPJ Breast Cancer. 9:512023. View Article : Google Scholar : | |
Weiss F, Hughes L, Fu Y, Bardy C, Halliday GM and Dzamko N: Astrocytes contribute to toll-like receptor 2-mediated neurodegeneration and alpha-synuclein pathology in a human midbrain Parkinson's model. Transl Neurodegener. 13:622024. View Article : Google Scholar : PubMed/NCBI | |
Sun L, Jiang WW, Wang Y, Yuan YS, Rong Z, Wu J, Fan Y, Lu M and Zhang KZ: Phosphorylated α-synuclein aggregated in Schwann cells exacerbates peripheral neuroinflammation and nerve dysfunction in Parkinson's disease through TLR2/NF-κB pathway. Cell Death Discov. 7:2892021. View Article : Google Scholar | |
Wendimu MY and Hooks SB: Microglia phenotypes in aging and neurodegenerative diseases. Cells. 11:20192022. View Article : Google Scholar | |
Kettenmann H, Kirchhoff F and Verkhratsky A: Microglia: New roles for the synaptic stripper. Neuron. 77:10–18. 2013. View Article : Google Scholar | |
Platanitis E and Decker T: Regulatory networks involving STATs, IRFs, and NFκB in inflammation. Front Immunol. 9:25422018. View Article : Google Scholar | |
Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, et al: CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 11:155–161. 2010. View Article : Google Scholar : | |
Wang Y, Wang YC and Ma J: Effects of electroacupuncture on Sirt3/NLRP3/GSDMD signaling pathway in the substantia nigra of midbrain of rats with Parkinson's disease. Zhen Ci Yan Jiu. 49:384–390. 2024.In Chinese. | |
Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, et al: TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS. Cell. 183:636–649.e18. 2020. View Article : Google Scholar : PubMed/NCBI | |
Becker LA, Huang B, Bieri G, Ma R, Knowles DA, Jafar-Nejad P, Messing J, Kim HJ, Soriano A, Auburger G, et al: Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 544:367–371. 2017. View Article : Google Scholar : PubMed/NCBI | |
Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, et al: A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 122:1377–1392. 2012. View Article : Google Scholar : | |
Hanslik KL and Ulland TK: The role of microglia and the Nlrp3 inflammasome in Alzheimer's disease. Front Neurol. 11:5707112020. View Article : Google Scholar : | |
Bolos M, Llorens-Martin M, Perea JR, Jurado-Arjona J, Rabano A, Hernandez F and Avila J: Absence of CX3CR1 impairs the internalization of Tau by microglia. Mol Neurodegener. 12:592017. View Article : Google Scholar : | |
Chidambaram H, Das R and Chinnathambi S: Interaction of Tau with the chemokine receptor, CX3CR1 and its effect on microglial activation, migration and proliferation. Cell Biosci. 10:1092020. View Article : Google Scholar | |
Wilton DK, Mastro K, Heller MD, Gergits FW, Willing CR, Fahey JB, Frouin A, Daggett A, Gu X, Kim YA, et al: Microglia and complement mediate early corticostriatal synapse loss and cognitive dysfunction in Huntington's disease. Nat Med. 29:2866–2884. 2023. View Article : Google Scholar | |
Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, Merry KM, Shi Q, Rosenthal A, Barres BA, et al: Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 352:712–716. 2016. View Article : Google Scholar : | |
Kim A, Garcia-Garcia E, Straccia M, Comella-Bolla A, Miguez A, Masana M, Alberch J, Canals JM and Rodriguez MJ: Reduced fractalkine levels lead to striatal synaptic plasticity deficits in Huntington's disease. Front Cell Neurosci. 14:1632020. View Article : Google Scholar | |
Logan T, Simon MJ, Rana A, Cherf GM, Srivastava A, Davis SS, Low RLY, Chiu CL, Fang M, Huang F, et al: Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic. Cell. 184:4651–4668.e25. 2021. View Article : Google Scholar | |
Mata-Martinez E, Diaz-Munoz M and Vazquez-Cuevas FG: Glial cells and brain diseases: Inflammasomes as relevant pathological entities. Front Cell Neurosci. 16:9295292022. View Article : Google Scholar : | |
Xu P, Zhang X, Liu Q, Xie Y, Shi X, Chen J, Li Y, Guo H, Sun R, Hong Y, et al: Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke. Cell Death Dis. 10:5552019. View Article : Google Scholar : | |
Qin Q, Teng Z, Liu C, Li Q, Yin Y and Tang Y: TREM2, microglia, and Alzheimer's disease. Mech Ageing Dev. 195:1114382021. View Article : Google Scholar | |
Caldeira C, Cunha C, Vaz AR, Falcao AS, Barateiro A, Seixas E, Fernandes A and Brites D: Key Aging-associated alterations in primary microglia response to Beta-amyloid stimulation. Front Aging Neurosci. 9:2772017. View Article : Google Scholar : PubMed/NCBI | |
Condello C, Yuan P, Schain A and Grutzendler J: Microglia Constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nat Commun. 6:61762015. View Article : Google Scholar | |
Feng W, Zhang Y, Wang Z, Xu H, Wu T, Marshall C, Gao J and Xiao M: Microglia Prevent beta-amyloid plaque formation in the early stage of an Alzheimer's disease mouse model with suppression of glymphatic clearance. Alzheimers Res Ther. 12:1252020. View Article : Google Scholar | |
Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O'Loughlin E, Xu Y, Fanek Z, et al: The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 47:566–581.e9. 2017. View Article : Google Scholar : | |
Felsky D, Patrick E, Schneider JA, Mostafavi S, Gaiteri C, Patsopoulos N, Bennett DA and De Jager PL: Polygenic analysis of inflammatory disease variants and effects on microglia in the aging brain. Mol Neurodegener. 13:382018. View Article : Google Scholar | |
Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J, Fitzgerald KC, Song A, Liu P, Lin JP, et al: A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature. 597:709–714. 2021. View Article : Google Scholar : PubMed/NCBI | |
Werneburg S, Jung J, Kunjamma RB, Ha SK, Luciano NJ, Willis CM, Gao G, Biscola NP, Havton LA, Crocker SJ, et al: Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease. Immunity. 52:167–182.e7. 2020. View Article : Google Scholar : | |
Ellrichmann G, Reick C, Saft C and Linker RA: The role of the immune system in Huntington's disease. Clin Dev Immunol. 2013:5412592013. View Article : Google Scholar : PubMed/NCBI | |
Creus-Muncunill J and Ehrlich ME: Cell-Autonomous and Non-cell-autonomous pathogenic mechanisms in Huntington's disease: Insights from in vitro and in vivo models. Neurotherapeutics. 16:957–978. 2019. View Article : Google Scholar | |
Udeochu JC, Amin S, Huang Y, Fan L, Torres ERS, Carling GK, Liu B, McGurran H, Coronas-Samano G, Kauwe G, et al: Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience. Nat Neurosci. 26:737–750. 2023. View Article : Google Scholar : PubMed/NCBI | |
Hu Y, Fryatt GL, Ghorbani M, Obst J, Menassa DA, Martin-Estebane M, Muntslag TAO, Olmos-Alonso A, Guerrero-Carrasco M, Thomas D, et al: Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology. Cell Rep. 35:1092282021. View Article : Google Scholar | |
Yamamoto M, Kiyota T, Walsh SM, Liu J, Kipnis J and Ikezu T: Cytokine-mediated inhibition of fibrillar amyloid-beta peptide degradation by human mononuclear phagocytes. J Immunol. 181:3877–3886. 2008. View Article : Google Scholar | |
Han F, Perrin RJ, Wang Q, Wang Y, Perlmutter JS, Morris JC, Benzinger TLS and Xu J: Neuroinflammation and Myelin Status in Alzheimer's disease, Parkinson's disease, and normal aging brains: A small sample study. Parkinsons Dis. 2019:79754072019.PubMed/NCBI | |
Jurga AM, Paleczna M and Kuter KZ: Overview of general and discriminating markers of differential microglia phenotypes. Front Cell Neurosci. 14:1982020. View Article : Google Scholar : | |
Gadani SP, Cronk JC, Norris GT and Kipnis J: IL-4 in the brain: A cytokine to remember. J Immunol. 189:4213–4219. 2012. View Article : Google Scholar | |
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Munch AE, Chung WS, Peterson TC, et al: Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 541:481–487. 2017. View Article : Google Scholar | |
Tecchio C, Micheletti A and Cassatella MA: Neutrophil-derived cytokines: Facts beyond expression. Front Immunol. 5:5082014. View Article : Google Scholar : PubMed/NCBI | |
Kummer MP, Hermes M, Delekarte A, Hammerschmidt T, Kumar S, Terwel D, Walter J, Pape HC, König S, Roeber S, et al: Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation. Neuron. 71:833–844. 2011. View Article : Google Scholar : PubMed/NCBI | |
Wang WY, Tan MS, Yu JT and Tan L: Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. Ann Transl Med. 3:1362015.PubMed/NCBI | |
Sheffield LG, Marquis JG and Berman NE: Regional distribution of cortical microglia parallels that of neurofibrillary tangles in Alzheimer's disease. Neurosci Lett. 285:165–168. 2000. View Article : Google Scholar | |
Venegas C and Heneka MT: Danger-associated molecular patterns in Alzheimer's disease. J Leukoc Biol. 101:87–98. 2017. View Article : Google Scholar | |
Jha MK, Jo M, Kim JH and Suk K: Microglia-astrocyte crosstalk: An intimate molecular conversation. Neuroscientist. 25:227–240. 2019. View Article : Google Scholar | |
Hanisch UK and Kettenmann H: Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 10:1387–1394. 2007. View Article : Google Scholar | |
Valdearcos M, Douglass JD, Robblee MM, Dorfman MD, Stifler DR, Bennett ML, Gerritse I, Fasnacht R, Barres BA, Thaler JP and Koliwad SK: Microglial inflammatory signaling orchestrates the hypothalamic immune response to dietary excess and mediates obesity susceptibility. Cell Metab. 26:185–197.e3. 2017. View Article : Google Scholar : PubMed/NCBI | |
Doens D and Fernandez PL: Microglia receptors and their implications in the response to amyloid β for Alzheimer's disease pathogenesis. J Neuroinflammation. 11:482014. View Article : Google Scholar | |
Kim E, Tolhurst AT, Qin LY, Chen XY, Febbraio M and Cho S: CD36/fatty acid translocase, an inflammatory mediator, is involved in hyperlipidemia-induced exacerbation in ischemic brain injury. J Neurosci. 28:4661–4670. 2008. View Article : Google Scholar : PubMed/NCBI | |
Gao D, Ashraf MZ, Kar NS, Lin D, Sayre LM and Podrez EA: Structural basis for the recognition of oxidized phospholipids in oxidized low density lipoproteins by class B scavenger receptors CD36 and SR-BI. J Biol Chem. 285:4447–4454. 2010. View Article : Google Scholar : | |
Coraci IS, Husemann J, Berman JW, Hulette C, Dufour JH, Campanella GK, Luster AD, Silverstein SC and El-Khoury JB: CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am J Pathol. 160:101–112. 2002. View Article : Google Scholar | |
Yamanaka M, Ishikawa T, Griep A, Axt D, Kummer MP and Heneka MT: PPARγ/RXRα-induced and CD36-mediated microglial amyloid-β phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J Neurosci. 32:17321–17331. 2012. View Article : Google Scholar : PubMed/NCBI | |
Sheedy FJ, Grebe A, Rayner KJ, Kalantari P, Ramkhelawon B, Carpenter SB, Becker CE, Ediriweera HN, Mullick AE, Golenbock DT, et al: CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat Immunol. 14:812–820. 2013. View Article : Google Scholar : | |
Cantuti-Castelvetri L, Fitzner D, Bosch-Queralt M, Weil MT, Su M, Sen P, Ruhwedel T, Mitkovski M, Trendelenburg G, Lütjohann D, et al: Defective cholesterol clearance limits remyelination in the aged central nervous system. Science. 359:684–688. 2018. View Article : Google Scholar | |
Yeh FL, Wang Y, Tom I, Gonzalez LC and Sheng M: TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of Amyloid-beta by microglia. Neuron. 91:328–340. 2016. View Article : Google Scholar | |
Lessard CB, Malnik SL, Zhou Y, Ladd TB, Cruz PE, Ran Y, Mahan TE, Chakrabaty P, Holtzman DM, Ulrich JD, et al: High-affinity interactions and signal transduction between Aβ oligomers and TREM2. EMBO Mol Med. 10:e90272018. View Article : Google Scholar | |
Beisiegel U, Weber W and Bengtsson-Olivecrona G: Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. Proc Natl Acad Sci USA. 88:8342–8346. 1991. View Article : Google Scholar | |
Gao Y, Vidal-Itriago A, Kalsbeek MJ, Layritz C, Garcia-Caceres C, Tom RZ, Eichmann TO, Vaz FM, Houtkooper RH, Van der Wel N, et al: Lipoprotein lipase maintains microglial innate immunity in obesity. Cell Rep. 20:3034–3042. 2017. View Article : Google Scholar : PubMed/NCBI | |
Aflaki E, Radovic B, Chandak PG, Kolb D, Eisenberg T, Ring J, Fertschai I, Uellen A, Wolinski H, Kohlwein SD, et al: Triacylglycerol accumulation activates the mitochondrial apoptosis pathway in macrophages. J Biol Chem. 286:7418–7428. 2011. View Article : Google Scholar : PubMed/NCBI | |
Weinger JG, Brosnan CF, Loudig O, Goldberg MF, Macian F, Arnett HA, Prieto AL, Tsiperson V and Shafit-Zagardo B: Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during experimental autoimmune encephalomyelitis. J Neuroinflammation. 8:492011. View Article : Google Scholar : | |
Shirotani K, Hori Y, Yoshizaki R, Higuchi E, Colonna M, Saito T, Hashimoto S, Saito T, Saido TC and Iwata N: Aminophospholipids are Signal-transducing TREM2 ligands on apoptotic cells. Sci Rep. 9:75082019. View Article : Google Scholar : | |
Bogie JF, Jorissen W, Mailleux J, Nijland PG, Zelcer N, Vanmierlo T, Van Horssen J, Stinissen P, Hellings N and Hendriks JJ: Myelin alters the inflammatory phenotype of macrophages by activating PPARs. Acta Neuropathol Commun. 1:432013. View Article : Google Scholar | |
Bogie JF, Timmermans S, Huynh-Thu VA, Irrthum A, Smeets HJ, Gustafsson JA, Steffensen KR, Mulder M, Stinissen P, Hellings N and Hendriks JJ: Myelin-derived lipids modulate macrophage activity by liver X receptor activation. PLoS One. 7:e449982012. View Article : Google Scholar : PubMed/NCBI | |
Safaiyan S, Kannaiyan N, Snaidero N, Brioschi S, Biber K, Yona S, Edinger AL, Jung S, Rossner MJ and Simons M: Age-related myelin degradation burdens the clearance function of microglia during aging. Nat Neurosci. 19:995–998. 2016. View Article : Google Scholar | |
Gabande-Rodriguez E, Perez-Canamas A, Soto-Huelin B, Mitroi DN, Sanchez-Redondo S, Martinez-Saez E, Venero C, Peinado H and Ledesma MD: Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders. EMBO J. 38:e995532019. View Article : Google Scholar | |
Carta AR and Simuni T: Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson's disease. Expert Opin Investig Drugs. 24:219–227. 2015. View Article : Google Scholar | |
Pioglitazone in early Parkinson's disease: A phase 2, multicentre, double-blind, randomised trial. Lancet Neurol. 14:795–803. 2015. View Article : Google Scholar | |
Huyghe S, Mannaerts GP, Baes M and Van Veldhoven PP: Peroxisomal multifunctional protein-2: The enzyme, the patients and the knockout mouse model. Biochim Biophys Acta. 1761:973–994. 2006. View Article : Google Scholar | |
Gong Y, Sasidharan N, Laheji F, Frosch M, Musolino P, Tanzi R, Kim DY, Biffi A, El Khoury J and Eichler F: Microglial dysfunction as a key pathological change in adrenomyeloneuropathy. Ann Neurol. 82:813–827. 2017. View Article : Google Scholar : PubMed/NCBI | |
Beckers L, Geric I, Stroobants S, Beel S, Van Damme P, D'Hooge R and Baes M: Microglia lacking a peroxisomal β-oxidation enzyme chronically alter their inflammatory profile without evoking neuronal and behavioral deficits. J Neuroinflammation. 16:612019. View Article : Google Scholar | |
Verheijden S, Beckers L, Casazza A, Butovsky O, Mazzone M and Baes M: Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal β-oxidation deficiency. Glia. 63:1606–1620. 2015. View Article : Google Scholar | |
Sangineto M, Ciarnelli M, Cassano T, Radesco A, Moola A, Bukke VN, Romano A, Villani R, Kanwal H, Capitanio N, et al: Metabolic reprogramming in inflammatory microglia indicates a potential way of targeting inflammation in Alzheimer's disease. Redox Biol. 66:1028462023. View Article : Google Scholar : PubMed/NCBI | |
Meiser J, Kramer L, Sapcariu SC, Battello N, Ghelfi J, D'Herouel AF, Skupin A and Hiller K: Pro-inflammatory macrophages sustain pyruvate oxidation through pyruvate dehydrogenase for the synthesis of itaconate and to enable cytokine expression. J Biol Chem. 291:3932–3946. 2016. View Article : Google Scholar : | |
Lauterbach MA, Hanke JE, Serefidou M, Mangan MSJ, Kolbe CC, Hess T, Rothe M, Kaiser R, Hoss F, Gehlen J, et al: Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase. Immunity. 51:997–1011.e7. 2019. View Article : Google Scholar : PubMed/NCBI | |
Plastira I, Bernhart E, Joshi L, Koyani CN, Strohmaier H, Reicher H, Malle E and Sattler W: MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia. J Neuroinflammation. 17:1272020. View Article : Google Scholar : | |
Huang YL, Morales-Rosado J, Ray J, Myers TG, Kho T, Lu M and Munford RS: Toll-like receptor agonists promote prolonged triglyceride storage in macrophages. J Biol Chem. 289:3001–3012. 2014. View Article : Google Scholar : | |
Palmieri EM, Gonzalez-Cotto M, Baseler WA, Davies LC, Ghesquiere B, Maio N, Rice CM, Rouault TA, Cassel T, Higashi RM, et al: Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase. Nat Commun. 11:6982020. View Article : Google Scholar | |
Rosas-Ballina M, Guan XL, Schmidt A and Bumann D: Classical activation of macrophages leads to lipid droplet formation without de novo fatty acid synthesis. Front Immunol. 11:1312020. View Article : Google Scholar : PubMed/NCBI | |
Bailey AP, Koster G, Guillermier C, Hirst EM, MacRae JI, Lechene CP, Postle AD and Gould AP: Antioxidant role for lipid droplets in a stem cell niche of drosophila. Cell. 163:340–353. 2015. View Article : Google Scholar : PubMed/NCBI | |
Khatchadourian A, Bourque SD, Richard VR, Titorenko VI and Maysinger D: Dynamics and regulation of lipid droplet formation in lipopolysaccharide (LPS)-stimulated microglia. Biochim Biophys Acta. 1821:607–617. 2012. View Article : Google Scholar : PubMed/NCBI | |
Marschallinger J, Iram T, Zardeneta M, Lee SE, Lehallier B, Haney MS, Pluvinage JV, Mathur V, Hahn O, Morgens DW, et al: Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nat Neurosci. 23:194–208. 2020. View Article : Google Scholar : PubMed/NCBI | |
Bogie JFJ, Grajchen E, Wouters E, Corrales AG, Dierckx T, Vanherle S, Mailleux J, Gervois P, Wolfs E, Dehairs J, et al: Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain. J Exp Med. 217:e201916602020. View Article : Google Scholar : PubMed/NCBI | |
Szatmari I, Torocsik D, Agostini M, Nagy T, Gurnell M, Barta E, Chatterjee K and Nagy L: PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism. Blood. 110:3271–3280. 2007. View Article : Google Scholar | |
Schonfeld P and Reiser G: Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration. Neurochem Int. 109:68–77. 2017. View Article : Google Scholar : PubMed/NCBI | |
Li LO, Klett EL and Coleman RA: Acyl-CoA synthesis, lipid metabolism and lipotoxicity. Biochim Biophys Acta. 1801:246–251. 2010. View Article : Google Scholar : | |
Fonteh AN, Cipolla M, Chiang J, Arakaki X and Harrington MG: Human cerebrospinal fluid fatty acid levels differ between supernatant fluid and brain-derived nanoparticle fractions, and are altered in Alzheimer's disease. PLoS One. 9:e1005192014. View Article : Google Scholar | |
Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA and Morris MC: Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 29:691–697. 2012. View Article : Google Scholar | |
Snowden SG, Ebshiana AA, Hye A, An Y, Pletnikova O, O'Brien R, Troncoso J, Legido-Quigley C and Thambisetty M: Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. PLoS Med. 14:e10022662017. View Article : Google Scholar : | |
Belkouch M, Hachem M, Elgot A, Lo Van A, Picq M, Guichardant M, Lagarde M and Bernoud-Hubac N: The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer's disease. J Nutr Biochem. 38:1–11. 2016. View Article : Google Scholar | |
Fonteh AN, Cipolla M, Chiang AJ, Edminster SP, Arakaki X and Harrington MG: Polyunsaturated fatty acid composition of cerebrospinal fluid fractions shows their contribution to cognitive resilience of a Pre-symptomatic Alzheimer's disease cohort. Front Physiol. 11:832020. View Article : Google Scholar : PubMed/NCBI | |
Prasad MR, Lovell MA, Yatin M, Dhillon H and Markesbery WR: Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem Res. 23:81–88. 1998. View Article : Google Scholar | |
Sebastiao AM, Colino-Oliveira M, Assaife-Lopes N, Dias RB and Ribeiro JA: Lipid rafts, synaptic transmission and plasticity: Impact in Age-related neurodegenerative diseases. Neuropharmacology. 64:97–107. 2013. View Article : Google Scholar | |
Sezgin E, Levental I, Mayor S and Eggeling C: The mystery of membrane organization: Composition, regulation and roles of lipid rafts. Nat Rev Mol Cell Biol. 18:361–374. 2017. View Article : Google Scholar : | |
Martin V, Fabelo N, Santpere G, Puig B, Marin R, Ferrer I and Diaz M: Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex. J Alzheimers Dis. 19:489–502. 2010. View Article : Google Scholar | |
Fabelo N, Martin V, Marin R, Moreno D, Ferrer I and Diaz M: Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer's disease and facilitates APP/BACE1 interactions. Neurobiol Aging. 35:1801–1812. 2014. View Article : Google Scholar | |
Filippov V, Song MA, Zhang K, Vinters HV, Tung S, Kirsch WM, Yang J and Duerksen-Hughes PJ: Increased ceramide in brains with Alzheimer's and other neurodegenerative diseases. J Alzheimers Dis. 29:537–547. 2012. View Article : Google Scholar | |
Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC and Mattson MP: Involvement of oxidative Stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci USA. 101:2070–2075. 2004. View Article : Google Scholar : PubMed/NCBI | |
Han X, M Holtzman D, McKeel DW Jr, Kelley J and Morris JC: Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: Potential role in disease pathogenesis. J Neurochem. 82:809–818. 2002. View Article : Google Scholar | |
He X, Huang Y, Li B, Gong CX and Schuchman EH: Deregulation of sphingolipid metabolism in Alzheimer's disease. Neurobiol Aging. 31:398–408. 2010. View Article : Google Scholar : | |
Soderberg M, Edlund C, Alafuzoff I, Kristensson K and Dallner G: Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type. J Neurochem. 59:1646–1653. 1992. View Article : Google Scholar : PubMed/NCBI | |
Siskind LJ: Mitochondrial ceramide and the induction of apoptosis. J Bioenerg Biomembr. 37:143–153. 2005. View Article : Google Scholar : PubMed/NCBI | |
Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N and Schneider J: Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 60:940–946. 2003. View Article : Google Scholar : PubMed/NCBI | |
Grimm MO, Grimm HS, Pätzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Müller U, Shen J and Hartmann T: Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol. 7:1118–1123. 2005. View Article : Google Scholar : PubMed/NCBI | |
Cheng H, Wang M, Li JL, Cairns NJ and Han X: Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer's disease: An early event in disease pathogenesis. J Neurochem. 127:733–738. 2013. View Article : Google Scholar : PubMed/NCBI | |
Couttas TA, Kain N, Suchowerska AK, Quek LE, Turner N, Fath T, Garner B and Don AS: Loss of ceramide synthase 2 activity, necessary for myelin biosynthesis, precedes tau pathology in the cortical pathogenesis of Alzheimer's disease. Neurobiol Aging. 43:89–100. 2016. View Article : Google Scholar | |
Nasrabady SE, Rizvi B, Goldman JE and Brickman AM: White matter changes in Alzheimer's disease: A focus on myelin and oligodendrocytes. Acta Neuropathol Commun. 6:222018. View Article : Google Scholar : PubMed/NCBI | |
Heverin M, Bogdanovic N, Lutjohann D, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B and Bjorkhem I: Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J Lipid Res. 45:186–193. 2004. View Article : Google Scholar | |
Popp J, Meichsner S, Kolsch H, Lewczuk P, Maier W, Kornhuber J, Jessen F and Lutjohann D: Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease. Biochem Pharmacol. 86:37–42. 2013. View Article : Google Scholar | |
Liu Y, Zhong X, Shen J, Jiao L, Tong J, Zhao W, Du K, Gong S, Liu M and Wei M: Elevated serum TC and LDL-C levels in Alzheimer's disease and mild cognitive impairment: A meta-analysis study. Brain Res. 1727:1465542020. View Article : Google Scholar | |
Zhang J and Liu Q: Cholesterol metabolism and homeostasis in the brain. Protein Cell. 6:254–264. 2015. View Article : Google Scholar : PubMed/NCBI | |
Tajima Y, Ishikawa M, Maekawa K, Murayama M, Senoo Y, Nishimaki-Mogami T, Nakanishi H, Ikeda K, Arita M and Taguchi R: Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease. Lipids Health Dis. 12:682013. View Article : Google Scholar | |
Bhattacharyya R, Barren C and Kovacs DM: Palmitoylation of amyloid precursor protein regulates amyloidogenic processing in lipid rafts. J Neurosci. 33:11169–11183. 2013. View Article : Google Scholar : | |
Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA and Hansen SB: Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proc Natl Acad Sci USA. 118:e21021911182021. View Article : Google Scholar | |
Qi G, Mi Y, Shi X, Gu H, Brinton RD and Yin F: ApoE4 impairs Neuron-astrocyte coupling of fatty acid metabolism. Cell Rep. 34:1085722021. View Article : Google Scholar : | |
Zhao J, Davis MD, Martens YA, Shinohara M, Graff-Radford NR, Younkin SG, Wszolek ZK, Kanekiyo T and Bu G: APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes. Hum Mol Genet. 26:2690–2700. 2017. View Article : Google Scholar | |
Kober DL and Brett TJ: TREM2-ligand interactions in health and disease. J Mol Biol. 429:1607–1629. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gouna G, Klose C, Bosch-Queralt M, Liu L, Gokce O, Schifferer M, Cantuti-Castelvetri L and Simons M: TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination. J Exp Med. 218:e202102272021. View Article : Google Scholar : | |
Basil MC and Levy BD: Specialized Pro-resolving mediators: Endogenous regulators of infection and inflammation. Nat Rev Immunol. 16:51–67. 2016. View Article : Google Scholar | |
Whittington RA, Planel E and Terrando N: Impaired resolution of inflammation in Alzheimer's disease: A review. Front Immunol. 8:14642017. View Article : Google Scholar | |
Emre C, Hjorth E, Bharani K, Carroll S, Granholm AC and Schultzberg M: Receptors for Pro-resolving mediators are increased in Alzheimer's disease brain. Brain Pathol. 30:614–640. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhu M, Wang X, Hjorth E, Colas RA, Schroeder L, Granholm AC, Serhan CN and Schultzberg M: Pro-resolving lipid mediators improve neuronal survival and increase Aβ42 phagocytosis. Mol Neurobiol. 53:2733–2749. 2016. View Article : Google Scholar | |
Wang X, Zhu M, Hjorth E, Cortes-Toro V, Eyjolfsdottir H, Graff C, Nennesmo I, Palmblad J, Eriksdotter M, et al: Resolution of inflammation is altered in Alzheimer's disease. Alzheimers Dement. 11:40–50. e1–e2. 2015. View Article : Google Scholar | |
Malaplate-Armand C, Florent-Bechard S, Youssef I, Koziel V, Sponne I, Kriem B, Leininger-Muller B, Olivier JL, Oster T and Pillot T: Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway. Neurobiol Dis. 23:178–189. 2006. View Article : Google Scholar : PubMed/NCBI | |
Prasad VV, Nithipatikom K and Harder DR: Ceramide elevates 12-hydroxyeicosatetraenoic acid levels and upregulates 12-lipoxygenase in rat primary hippocampal cell cultures containing predominantly astrocytes. Neurochem Int. 53:220–229. 2008. View Article : Google Scholar | |
Assayag K, Yakunin E, Loeb V, Selkoe DJ and Sharon R: Polyunsaturated fatty acids induce alpha-synuclein-related pathogenic changes in neuronal cells. Am J Pathol. 171:2000–2011. 2007. View Article : Google Scholar | |
Flores-Leon M and Outeiro TF: More than meets the eye in Parkinson's disease and other synucleinopathies: From proteinopathy to lipidopathy. Acta Neuropathol. 146:369–385. 2023. View Article : Google Scholar | |
Yakunin E, Loeb V, Kisos H, Biala Y, Yehuda S, Yaari Y, Selkoe DJ and Sharon R: Α-synuclein neuropathology is controlled by nuclear hormone receptors and enhanced by docosahexaenoic acid in a mouse model for Parkinson's disease. Brain Pathol. 22:280–294. 2012. View Article : Google Scholar | |
Galvagnion C: The role of lipids interacting with α-synuclein in the pathogenesis of Parkinson's disease. J Parkinsons Dis. 7:433–450. 2017. View Article : Google Scholar | |
Garcia-Sanz P, MFG Aerts J and Moratalla R: The role of cholesterol in alpha-synuclein and lewy body pathology in GBA1 Parkinson's disease. Mov Disord. 36:1070–1085. 2021. View Article : Google Scholar | |
Paslawski W, Zareba-Paslawska J, Zhang X, Holzl K, Wadensten H, Shariatgorji M, Janelidze S, Hansson O, Forsgren L, Andrén PE and Svenningsson P: α-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients. Proc Natl Acad Sci USA. 116:15226–15235. 2019. View Article : Google Scholar | |
Kim HE, Grant AR, Simic MS, Kohnz RA, Nomura DK, Durieux J, Riera CE, Sanchez M, Kapernick E, Wolff S and Dillin A: Lipid biosynthesis coordinates a mitochondrial-to-Cytosolic stress response. Cell. 166:1539–1552.e16. 2016. View Article : Google Scholar | |
Stein D, Mizrahi A, Golova A, Saretzky A, Venzor AG, Slobodnik Z, Kaluski S, Einav M, Khrameeva E and Toiber D: Aging and pathological aging signatures of the brain: Through the focusing lens of SIRT6. Aging (Albany NY). 13:6420–6441. 2021. View Article : Google Scholar | |
Smirnov D, Eremenko E, Stein D, Kaluski S, Jasinska W, Cosentino C, Martinez-Pastor B, Brotman Y, Mostoslavsky R, Khrameeva E and Toiber D: SIRT6 is a key regulator of mitochondrial function in the brain. Cell Death Dis. 14:352023. View Article : Google Scholar : PubMed/NCBI | |
Ghio S, Kamp F, Cauchi R, Giese A and Vassallo N: Interaction of α-synuclein with biomembranes in Parkinson's disease-role of cardiolipin. Prog Lipid Res. 61:73–82. 2016. View Article : Google Scholar | |
Chu CT, Ji J, Dagda RK, Jiang JF, Tyurina YY, Kapralov AA, Tyurin VA, Yanamala N, Shrivastava IH, Mohammadyani D, et al: Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol. 15:1197–1205. 2013. View Article : Google Scholar : PubMed/NCBI | |
Doblado L, Lueck C, Rey C, Samhan-Arias AK, Prieto I, Stacchiotti A and Monsalve M: Mitophagy in human diseases. Int J Mol Sci. 22:39032021. View Article : Google Scholar : | |
Rocha EM, Smith GA, Park E, Cao H, Graham AR, Brown E, McLean JR, Hayes MA, Beagan J, Izen SC, et al: Sustained systemic glucocerebrosidase inhibition induces Brain α-synuclein aggregation, microglia and complement C1q activation in mice. Antioxid Redox Signal. 23:550–564. 2015. View Article : Google Scholar : | |
Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, et al: Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 167:1469–1480.e12. 2016. View Article : Google Scholar | |
Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M and Nagatsu T: Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 180:147–150. 1994. View Article : Google Scholar | |
Moloney EB, Moskites A, Ferrari EJ, Isacson O and Hallett PJ: The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson's disease patients and increases after lysosomal stress. Neurobiol Dis. 120:1–11. 2018. View Article : Google Scholar : PubMed/NCBI | |
Rebeck GW: The role of APOE on lipid homeostasis and inflammation in normal brains. J Lipid Res. 58:1493–1499. 2017. View Article : Google Scholar | |
Atagi Y, Liu CC, Painter MM, Chen XF, Verbeeck C, Zheng H, Li X, Rademakers R, Kang SS, Xu H, et al: Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J Biol Chem. 290:26043–26050. 2015. View Article : Google Scholar : PubMed/NCBI | |
Herrera AJ, Castano A, Venero JL, Cano J and Machado A: The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system. Neurobiol Dis. 7:429–447. 2000. View Article : Google Scholar | |
Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ and Lee VM: Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci. 28:7687–7698. 2008. View Article : Google Scholar | |
Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, et al: Neuron-astrocyte metabolic coupling protects against Activity-induced fatty acid toxicity. Cell. 177:1522–1535.e14. 2019. View Article : Google Scholar : PubMed/NCBI | |
Braidy N, Gai WP, Xu YH, Sachdev P, Guillemin GJ, Jiang XM, Ballard JW, Horan MP, Fang ZM, Chong BH and Chan DK: Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts. Transl Neurodegener. 2:202013. View Article : Google Scholar : PubMed/NCBI | |
Sipione S, Rigamonti D, Valenza M, Zuccato C, Conti L, Pritchard J, Kooperberg C, Olson JM and Cattaneo E: Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses. Hum Mol Genet. 11:1953–1965. 2002. View Article : Google Scholar : PubMed/NCBI | |
Leoni V and Caccia C: Study of cholesterol metabolism in Huntington's disease. Biochem Biophys Res Commun. 446:697–701. 2014. View Article : Google Scholar | |
Karasinska JM and Hayden MR: Cholesterol metabolism in Huntington disease. Nat Rev Neurol. 7:561–572. 2011. View Article : Google Scholar : PubMed/NCBI | |
Leoni V and Caccia C: The impairment of cholesterol metabolism in Huntington disease. Biochim Biophys Acta. 1851:1095–1105. 2015. View Article : Google Scholar | |
Valenza M, Rigamonti D, Goffredo D, Zuccato C, Fenu S, Jamot L, Strand A, Tarditi A, Woodman B, Racchi M, et al: Dysfunction of the cholesterol biosynthetic pathway in Huntington's disease. J Neurosci. 25:9932–9939. 2005. View Article : Google Scholar : PubMed/NCBI | |
Wang N, Yvan-Charvet L, Lutjohann D, Mulder M, Vanmierlo T, Kim TW and Tall AR: ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain. FASEB J. 22:1073–1082. 2008. View Article : Google Scholar | |
Leoni V, Long JD, Mills JA, Di Donato S and Paulsen JS; PREDICT-HD study group: Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression. Neurobiol Dis. 55:37–43. 2013. View Article : Google Scholar : PubMed/NCBI | |
Tansey TR and Shechter I: Squalene synthase: Structure and regulation. Prog Nucleic Acid Res Mol Biol. 65:157–195. 2001. View Article : Google Scholar | |
Kreilaus F, Spiro AS, McLean CA, Garner B and Jenner AM: Evidence for altered cholesterol metabolism in Huntington's disease post mortem brain tissue. Neuropathol Appl Neurobiol. 42:535–546. 2016. View Article : Google Scholar | |
Valenza M, Leoni V, Tarditi A, Mariotti C, Bjorkhem I, Di Donato S and Cattaneo E: Progressive dysfunction of the cholesterol biosynthesis pathway in the R6/2 mouse model of Huntington's disease. Neurobiol Dis. 28:133–142. 2007. View Article : Google Scholar | |
Martin MG, Pfrieger F and Dotti CG: Cholesterol in brain disease: Sometimes determinant and frequently implicated. EMBO Rep. 15:1036–1052. 2014. View Article : Google Scholar : PubMed/NCBI | |
Valenza M, Leoni V, Karasinska JM, Petricca L, Fan J, Carroll J, Pouladi MA, Fossale E, Nguyen HP, Riess O, et al: Cholesterol defect is marked across multiple rodent models of Huntington's disease and is manifest in astrocytes. J Neurosci. 30:10844–10850. 2010. View Article : Google Scholar | |
Xu Z, He S, Begum MM and Han X: Myelin lipid alterations in neurodegenerative diseases: Landscape and pathogenic implications. Antioxid Redox Signal. 41:1073–1099. 2024. View Article : Google Scholar : PubMed/NCBI | |
Lawton KA, Brown MV, Alexander D, Li Z, Wulff JE, Lawson R, Jaffa M, Milburn MV, Ryals JA, Bowser R, et al: Plasma metabolomic biomarker panel to distinguish patients with amyotrophic lateral sclerosis from disease mimics. Amyotroph Lateral Scler Frontotemporal Degener. 15:362–370. 2014. View Article : Google Scholar | |
Goutman SA, Boss J, Guo K, Alakwaa FM, Patterson A, Kim S, Savelieff MG, Hur J and Feldman EL: Untargeted metabolomics yields insight into ALS disease mechanisms. J Neurol Neurosurg Psychiatry. 91:1329–1338. 2020. View Article : Google Scholar | |
Sol J, Jove M, Povedano M, Sproviero W, Dominguez R, Pinol-Ripoll G, Romero-Guevara R, Hye A, Al-Chalabi A, Torres P, et al: Lipidomic traits of plasma and cerebrospinal fluid in amyotrophic lateral sclerosis correlate with disease progression. Brain Commun. 3:fcab1432021. View Article : Google Scholar : PubMed/NCBI | |
Area-Gomez E, Larrea D, Yun T, Xu Y, Hupf J, Zandkarimi F, Chan RB and Mitsumoto H: Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders. Sci Rep. 11:135622021. View Article : Google Scholar | |
FernAndez-Eulate G, Ruiz-Sanz JI, Riancho J, ZufirIa M, GereNu G, FernAndez-TorrOn R, Poza-Aldea JJ, Ondaro J, Espinal JB, GonzÁlez-ChinchÓn G, et al: A comprehensive serum lipidome profiling of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 21:252–262. 2020. View Article : Google Scholar | |
Winkler EA, Sengillo JD, Sullivan JS, Henkel JS, Appel SH and Zlokovic BV: Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis. Acta Neuropathol. 125:111–120. 2013. View Article : Google Scholar | |
Waters S, Swanson MEV, Dieriks BV, Zhang YB, Grimsey NL, Murray HC, Turner C, Waldvogel HJ, Faull RLM, An J, et al: Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS. Acta Neuropathol Commun. 9:1442021. View Article : Google Scholar : PubMed/NCBI | |
Blasco H, Veyrat-Durebex C, Bocca C, Patin F, Vourc'h P, Kouassi Nzoughet J, Lenaers G, Andres CR, Simard G, Corcia P and Reynier P: Lipidomics reveals Cerebrospinal-Fluid signatures of ALS. Sci Rep. 7:176522017. View Article : Google Scholar | |
Patin F, Corcia P, Vourc'h P, Nadal-Desbarats L, Baranek T, Goossens JF, Marouillat S, Dessein AF, Descat A, Madji Hounoum B, et al: Omics to explore amyotrophic lateral sclerosis evolution: The central role of arginine and proline metabolism. Mol Neurobiol. 54:5361–5374. 2017. View Article : Google Scholar | |
Cutler RG, Pedersen WA, Camandola S, Rothstein JD and Mattson MP: Evidence that accumulation of ceramides and cholesterol esters mediates oxidative Stress-induced death of motor neurons in amyotrophic lateral sclerosis. Ann Neurol. 52:448–457. 2002. View Article : Google Scholar | |
Dodge JC, Jensen EH, Yu J, Sardi SP, Bialas AR, Taksir TV, Bangari DS and Shihabuddin LS: Neutral lipid cacostasis contributes to disease pathogenesis in amyotrophic lateral sclerosis. J Neurosci. 40:9137–9147. 2020. View Article : Google Scholar | |
Dodge JC, Treleaven CM, Pacheco J, Cooper S, Bao C, Abraham M, Cromwell M, Sardi SP, Chuang WL, Sidman RL, et al: Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis. Proc Natl Acad Sci USA. 112:8100–8105. 2015. View Article : Google Scholar : | |
Burg T, Rossaert E, Moisse M, Van Damme P and Van Den Bosch L: Histone deacetylase inhibition regulates lipid homeostasis in a mouse model of amyotrophic lateral sclerosis. Int J Mol Sci. 22:112242021. View Article : Google Scholar : | |
Chaves-Filho AB, Pinto IFD, Dantas LS, Xavier AM, Inague A, Faria RL, Medeiros MHG, Glezer I, Yoshinaga MY and Miyamoto S: Alterations in lipid metabolism of spinal cord linked to amyotrophic lateral sclerosis. Sci Rep. 9:116422019. View Article : Google Scholar : | |
Ramirez-Nunez O, Jove M, Torres P, Sol J, Fontdevila L, Romero-Guevara R, Andres-Benito P, Ayala V, Rossi C, Boada J, et al: Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study. J Neurochem. 158:482–499. 2021. View Article : Google Scholar | |
Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, Alahmady N, Renton AE, Topp SD, Gibbs JR, et al: Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis. JAMA Neurol. 78:1236–1248. 2021. View Article : Google Scholar | |
Mohassel P, Donkervoort S, Lone MA, Nalls M, Gable K, Gupta SD, Foley AR, Hu Y, Saute JAM, Moreira AL, et al: Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. Nat Med. 27:1197–1204. 2021. View Article : Google Scholar | |
Kim SM, Noh MY, Kim H, Cheon SY, Lee KM, Lee J, Cha E, Park KS, Lee KW, Sung JJ and Kim SH: 25-Hydroxycholesterol is involved in the pathogenesis of amyotrophic lateral sclerosis. Oncotarget. 8:11855–11867. 2017. View Article : Google Scholar : PubMed/NCBI | |
Dodge JC, Yu J, Sardi SP and Shihabuddin LS: Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis. Sci Rep. 11:8032021. View Article : Google Scholar : PubMed/NCBI | |
Kann O: The interneuron energy hypothesis: Implications for brain disease. Neurobiol Dis. 90:75–85. 2016. View Article : Google Scholar | |
Mauch DH, Nägler K, Schumacher S, Göritz C, Müller EC, Otto A and Pfrieger FW: CNS synaptogenesis promoted by Glia-derived cholesterol. Science. 294:1354–1357. 2001. View Article : Google Scholar | |
Foley P: Lipids in Alzheimer's disease: A century-old story. Biochim Biophys Acta. 1801:750–753. 2010. View Article : Google Scholar | |
Cai XT, Li H, Borch Jensen M, Maksoud E, Borneo J, Liang Y, Quake SR, Luo L, Haghighi P and Jasper H: Gut cytokines modulate olfaction through metabolic reprogramming of glia. Nature. 596:97–102. 2021. View Article : Google Scholar : PubMed/NCBI | |
den Brok MH, Raaijmakers TK, Collado-Camps E and Adema GJ: Lipid droplets as immune modulators in myeloid cells. Trends Immunol. 39:380–392. 2018. View Article : Google Scholar | |
Lee JY, Marian OC and Don AS: Defective lysosomal lipid catabolism as a common pathogenic mechanism for dementia. Neuromolecular Med. 23:1–24. 2021. View Article : Google Scholar | |
Lin CH, Liao LY, Yang TY, Chang YJ, Tung CW, Hsu SL and Hsueh CM: Microglia-derived adiposomes are potential targets for the treatment of ischemic stroke. Cell Mol Neurobiol. 39:591–604. 2019. View Article : Google Scholar | |
Chali F, Milior G, Marty S, Morin-Brureau M, Le Duigou C, Savary E, Blugeon C, Jourdren L and Miles R: Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate-treated mice. Eur J Neurosci. 50:1759–1778. 2019. View Article : Google Scholar | |
Astarita G, Jung KM, Vasilevko V, Dipatrizio NV, Martin SK, Cribbs DH, Head E, Cotman CW and Piomelli D: Elevated stearoyl-CoA desaturase in brains of patients with Alzheimer's disease. PLoS One. 6:e247772011. View Article : Google Scholar : PubMed/NCBI | |
Shibuya Y, Chang CC and Chang TY: ACAT1/SOAT1 as a therapeutic target for Alzheimer's disease. Future Med Chem. 7:2451–2467. 2015. View Article : Google Scholar | |
Lin YT, Seo J, Gao F, Feldman HM, Wen HL, Penney J, Cam HP, Gjoneska E, Raja WK, Cheng J, et al: APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC-derived brain cell types. Neuron. 98:1141–1154.e7. 2018. View Article : Google Scholar | |
Chen Y, Strickland MR, Soranno A and Holtzman DM: Apolipoprotein E: Structural Insights and Links to Alzheimer disease pathogenesis. Neuron. 109:205–221. 2021. View Article : Google Scholar | |
Yen JHJ and Yu ICI: The role of ApoE-mediated microglial lipid metabolism in brain aging and disease. Immunometabolism (Cobham). 5:e000182023. View Article : Google Scholar | |
Sienski G, Narayan P, Bonner JM, Kory N, Boland S, Arczewska AA, Ralvenius WT, Akay L, Lockshin E, He L, et al: APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia. Sci Transl Med. 13:eaaz45642021. View Article : Google Scholar : PubMed/NCBI | |
Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y, Jain BR, Bertelsen SE, Kapoor M, Marcora E, et al: Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell. 185:2213–2233.e25. 2022. View Article : Google Scholar : PubMed/NCBI | |
Victor MB, Leary N, Luna X, Meharena HS, Scannail AN, Bozzelli PL, Samaan G, Murdock MH, von Maydell D, Effenberger AH, et al: Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity. Cell Stem Cell. 29:1197–1212.e8. 2022. View Article : Google Scholar : PubMed/NCBI | |
Guglielmotto M, Monteleone D, Piras A, Valsecchi V, Tropiano M, Ariano S, Fornaro M, Vercelli A, Puyal J, Arancio O, et al: Aβ1-42 monomers or oligomers have different effects on autophagy and apoptosis. Autophagy. 10:1827–1843. 2014. View Article : Google Scholar : PubMed/NCBI | |
Baerends E, Soud K, Folke J, Pedersen AK, Henmar S, Konrad L, Lycas MD, Mori Y, Pakkenberg B, Woldbye DPD, et al: Modeling the early stages of Alzheimer's disease by administering intracerebroventricular injections of human native Aβ oligomers to rats. Acta Neuropathol Commun. 10:1132022. View Article : Google Scholar | |
Brown AJ and Jessup W: Oxysterols: Sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis. Mol Aspects Med. 30:111–122. 2009. View Article : Google Scholar | |
Chang JY, Chavis JA, Liu LZ and Drew PD: Cholesterol oxides induce programmed cell death in microglial cells. Biochem Biophys Res Commun. 249:817–821. 1998. View Article : Google Scholar | |
Liu J, Liu Y, Chen J, Hu C, Teng M, Jiao K, Shen Z, Zhu D, Yue J, Li Z and Li Y: The ROS-mediated activation of IL-6/STAT3 signaling pathway is involved in the 27-hydroxycholesterol-induced cellular senescence in nerve cells. Toxicol In Vitro. 45:10–18. 2017. View Article : Google Scholar : PubMed/NCBI | |
Simpson DSA and Oliver PL: ROS Generation in microglia: Understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants (Basel). 9:7432020. View Article : Google Scholar : PubMed/NCBI | |
Olsen BN, Schlesinger PH and Baker NA: Perturbations of membrane structure by cholesterol and cholesterol derivatives are determined by sterol orientation. J Am Chem Soc. 131:4854–4865. 2009. View Article : Google Scholar : PubMed/NCBI | |
Kauffman JM, Westerman PW and Carey MC: Fluorocholesterols, in contrast to hydroxycholesterols, exhibit interfacial properties similar to cholesterol. J Lipid Res. 41:991–1003. 2000. View Article : Google Scholar : PubMed/NCBI | |
Appelqvist H, Wäster P, Kågedal K and Öllinger K: The lysosome: From waste bag to potential therapeutic target. J Mol Cell Biol. 5:214–226. 2013. View Article : Google Scholar : PubMed/NCBI | |
Gosselet F, Saint-Pol J and Fenart L: Effects of oxysterols on the blood-brain barrier: Implications for Alzheimer's disease. Biochem Biophys Res Commun. 446:687–691. 2014. View Article : Google Scholar | |
Trompier D, Vejux A, Zarrouk A, Gondcaille C, Geillon F, Nury T, Savary S and Lizard G: Brain peroxisomes. Biochimie. 98:102–110. 2014. View Article : Google Scholar | |
Loving BA, Tang M, Neal MC, Gorkhali S, Murphy R, Eckel RH and Bruce KD: Lipoprotein lipase regulates microglial lipid droplet accumulation. Cells. 10:1982021. View Article : Google Scholar | |
Berghoff SA, Spieth L, Sun T, Hosang L, Schlaphoff L, Depp C, Düking T, Winchenbach J, Neuber J, Ewers D, et al: Microglia facilitate repair of demyelinated lesions via Post-squalene sterol synthesis. Nat Neurosci. 24:47–60. 2021. View Article : Google Scholar : | |
Ciesielska A, Matyjek M and Kwiatkowska K: TLR4 and CD14 trafficking and its influence on LPS-induced Pro-inflammatory signaling. Cell Mol Life Sci. 78:1233–1261. 2021. View Article : Google Scholar | |
Sheng JG, Bora SH, Xu G, Borchelt DR, Price DL and Koliatsos VE: Lipopolysaccharide-Induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid beta peptide in APPswe transgenic mice. Neurobiol Dis. 14:133–145. 2003. View Article : Google Scholar : PubMed/NCBI | |
Chen Y, Yin M, Cao X, Hu G and Xiao M: Pro- and Anti-inflammatory effects of high cholesterol diet on aged brain. Aging Dis. 9:374–390. 2018. View Article : Google Scholar : PubMed/NCBI | |
Iannucci J, Sen A and Grammas P: Isoform-specific effects of apolipoprotein E on markers of inflammation and toxicity in brain glia and neuronal cells in vitro. Curr Issues Mol Biol. 43:215–225. 2021. View Article : Google Scholar | |
Churchward MA and Todd KG: Statin treatment affects cytokine release and phagocytic activity in primary cultured microglia through two separable mechanisms. Mol Brain. 7:852014. View Article : Google Scholar : PubMed/NCBI | |
Tanaka N, Abe-Dohmae S, Iwamoto N, Fitzgerald ML and Yokoyama S: Helical apolipoproteins of High-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7. J Lipid Res. 51:2591–2599. 2010. View Article : Google Scholar : PubMed/NCBI | |
Aikawa T, Holm ML and Kanekiyo T: ABCA7 and pathogenic pathways of Alzheimer's disease. Brain Sci. 8:272018. View Article : Google Scholar : PubMed/NCBI | |
Dai W, Yao RM, Mi TY, Zhang LM, Wu HL, Cheng JB and Li YF: Cognition-enhancing effect of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in the 5 x FAD transgenic mouse model of Alzheimer's pathology. J Psychopharmacol. 36:1176–1187. 2022. View Article : Google Scholar : PubMed/NCBI | |
Bouhrara M, Reiter DA, Bergeron CM, Zukley LM, Ferrucci L, Resnick SM and Spencer RG: Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content. Alzheimers Dement. 14:998–1004. 2018. View Article : Google Scholar | |
Benitez A, Fieremans E, Jensen JH, Falangola MF, Tabesh A, Ferris SH and Helpern JA: White matter tract integrity metrics reflect the vulnerability of Late-myelinating tracts in Alzheimer's disease. Neuroimage Clin. 4:64–71. 2014. View Article : Google Scholar | |
Depp C, Sun T, Sasmita AO, Spieth L, Berghoff SA, Nazarenko T, Overhoff K, Steixner-Kumar AA, Subramanian S, Arinrad S, et al: Myelin dysfunction drives amyloid-β deposition in models of Alzheimer's disease. Nature. 618:349–357. 2023. View Article : Google Scholar : PubMed/NCBI | |
Mathys H, Davila-Velderrain J, Peng Z, Gao F, Mohammadi S, Young JZ, Menon M, He L, Abdurrob F, Jiang X, et al: Single-cell transcriptomic analysis of Alzheimer's disease. Nature. 570:332–337. 2019. View Article : Google Scholar : PubMed/NCBI | |
Saez-Atienzar S and Masliah E: Cellular senescence and Alzheimer disease: The egg and the chicken scenario. Nat Rev Neurosci. 21:433–444. 2020. View Article : Google Scholar : PubMed/NCBI | |
Lloyd AF and Miron VE: The Pro-remyelination properties of microglia in the central nervous system. Nat Rev Neurol. 15:447–458. 2019. View Article : Google Scholar | |
Cignarella F, Filipello F, Bollman B, Cantoni C, Locca A, Mikesell R, Manis M, Ibrahim A, Deng L, Benitez BA, et al: TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis. Acta Neuropathol. 140:513–534. 2020. View Article : Google Scholar : PubMed/NCBI | |
Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, et al: M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 16:1211–1218. 2013. View Article : Google Scholar : PubMed/NCBI | |
Lloyd AF, Davies CL, Holloway RK, Labrak Y, Ireland G, Carradori D, Dillenburg A, Borger E, Soong D, Richardson JC, et al: Central nervous system regeneration is driven by microglia necroptosis and repopulation. Nat Neurosci. 22:1046–1052. 2019. View Article : Google Scholar : | |
Mecha M, Yanguas-Casás N, Feliú A, Mestre L, Carrillo-Salinas F, Azcoitia I, Yong VW and Guaza C: The endocannabinoid 2-AG enhances spontaneous remyelination by targeting microglia. Brain Behav Immun. 77:110–126. 2019. View Article : Google Scholar | |
Wang X, Cao K, Sun X, Chen Y, Duan Z, Sun L, Guo L, Bai P, Sun D, Fan J, et al: Macrophages in spinal cord injury: Phenotypic and functional change from exposure to myelin debris. Glia. 63:635–651. 2015. View Article : Google Scholar : | |
Mrdjen D, Pavlovic A, Hartmann FJ, Schreiner B, Utz SG, Leung BP, Lelios I, Heppner FL, Kipnis J, Merkler D, et al: High-Dimensional Single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity. 48:5992018. View Article : Google Scholar | |
Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J, et al: Single-Cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity. 50:253–271.e6. 2019. View Article : Google Scholar | |
Zrzavy T, Hametner S, Wimmer I, Butovsky O, Weiner HL and Lassmann H: Loss of 'homeostatic' microglia and patterns of their activation in active multiple sclerosis. Brain. 140:1900–1913. 2017. View Article : Google Scholar : PubMed/NCBI | |
Locatelli G, Theodorou D, Kendirli A, Jordão MJC, Staszewski O, Phulphagar K, Cantuti-Castelvetri L, Dagkalis A, Bessis A, Simons M, et al: Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model. Nat Neurosci. 21:1196–1208. 2018. View Article : Google Scholar : PubMed/NCBI | |
Wlodarczyk A, Benmamar-Badel A, Cédile O, Jensen KN, Kramer I, Elsborg NB and Owens T: CSF1R stimulation promotes increased neuroprotection by CD11c+ microglia in EAE. Front Cell Neurosci. 12:5232018. View Article : Google Scholar | |
Yu Z, Sun D, Feng J, Tan W, Fang X, Zhao M, Zhao X, Pu Y, Huang A, Xiang Z, et al: MSX3 Switches microglia polarization and protects from Inflammation-induced demyelination. J Neurosci. 35:6350–6365. 2015. View Article : Google Scholar | |
Zabala A, Vazquez-Villoldo N, Rissiek B, Gejo J, Martin A, Palomino A, Perez-Samartín A, Pulagam KR, Lukowiak M, Capetillo-Zarate E, et al: P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. EMBO Mol Med. 10:e87432018. View Article : Google Scholar : | |
Brüne B, Dehne N, Grossmann N, Jung M, Namgaladze D, Schmid T, von Knethen A and Weigert A: Redox control of inflammation in macrophages. Antioxid Redox Signal. 19:595–637. 2013. View Article : Google Scholar | |
Conrad M, Kagan VE, Bayir H, Pagnussat GC, Head B, Traber MG and Stockwell BR: Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev. 32:602–619. 2018. View Article : Google Scholar : PubMed/NCBI | |
Wenzel SE, Tyurina YY, Zhao J, St Croix CM, Dar HH, Mao G, Tyurin VA, Anthonymuthu TS, Kapralov AA, Amoscato AA, et al: PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell. 171:628–641.e26. 2017. View Article : Google Scholar : PubMed/NCBI | |
Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB, et al: Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol. 13:81–90. 2017. View Article : Google Scholar | |
Anthonymuthu TS, Kenny EM, Shrivastava I, Tyurina YY, Hier ZE, Ting HC, Dar HH, Tyurin VA, Nesterova A, Amoscato AA, et al: Empowerment of 15-lipoxygenase catalytic competence in selective oxidation of membrane ETE-PE to ferroptotic death signals, HpETE-PE. J Am Chem Soc. 140:17835–17839. 2018. View Article : Google Scholar : PubMed/NCBI | |
Kapralov AA, Yang Q, Dar HH, Tyurina YY, Anthonymuthu TS, Kim R, St Croix CM, Mikulska-Ruminska K, Liu B, Shrivastava IH, et al: Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death. Nat Chem Biol. 16:278–290. 2020. View Article : Google Scholar : PubMed/NCBI | |
Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, et al: ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 13:91–98. 2017. View Article : Google Scholar | |
Zhou Y, Yang Y, Yi L, Pan M, Tang W and Duan H: Propofol mitigates Sepsis-induced brain injury by inhibiting ferroptosis via activation of the Nrf2/HO-1axis. Neurochem Res. 49:2131–2147. 2024. View Article : Google Scholar | |
Zhou X, Zhao R, Lv M, Xu X, Liu W, Li X, Gao Y, Zhao Z, Zhang Z, Li Y, et al: ACSL4 promotes microgliamediated neuroinflammation by regulating lipid metabolism and VGLL4 expression. Brain Behav Immun. 109:331–343. 2023. View Article : Google Scholar : PubMed/NCBI | |
Liang D, Minikes AM and Jiang X: Ferroptosis at the intersection of lipid metabolism and cellular signaling. Mol Cell. 82:2215–2227. 2022. View Article : Google Scholar : PubMed/NCBI | |
Wu H, Li N, Peng S, Fu H, Hu Z and Su L: Maresin1 improves hippocampal neuroinflammation and cognitive function in septic rats by activating the SLC7A11/GPX4 ferroptosis signaling pathway. Int Immunopharmacol. 131:1117922024. View Article : Google Scholar | |
Fernández-Mendívil C, Luengo E, Trigo-Alonso P, García-Magro N, Negredo P and López MG: Protective role of microglial HO-1 blockade in aging: Implication of iron metabolism. Redox Biol. 38:1017892021. View Article : Google Scholar | |
Gao S, Zhou L, Lu J, Fang Y, Wu H, Xu W, Pan Y, Wang J, Wang X, Zhang J and Shao A: Cepharanthine attenuates early brain injury after subarachnoid hemorrhage in mice via inhibiting 15-Lipoxygenase-1-Mediated microglia and endothelial cell ferroptosis. Oxid Med Cell Longev. 2022:42952082022. View Article : Google Scholar : | |
Strike SC, Carlisle A, Gibson EL and Dyall SC: A High Omega-3 fatty acid multinutrient supplement benefits cognition and mobility in older women: A randomized, Double-blind, Placebo-controlled pilot study. J Gerontol A Biol Sci Med Sci. 71:236–242. 2016. View Article : Google Scholar | |
Lee LK, Shahar S, Chin AV and Yusoff NA: Docosahexaenoic Acid-concentrated fish oil supplementation in subjects with mild cognitive impairment (MCI): A 12-month randomised, double-blind, placebo-controlled trial. Psychopharmacology (Berl). 225:605–612. 2013. View Article : Google Scholar | |
Serrano-Pozo A, Vega GL, Lütjohann D, Locascio JJ, Tennis MK, Deng A, Atri A, Hyman BT, Irizarry MC and Growdon JH: Effects of simvastatin on cholesterol metabolism and Alzheimer disease biomarkers. Alzheimer Dis Assoc Disord. 24:220–226. 2010. View Article : Google Scholar | |
Evans BA, Evans JE, Baker SP, Kane K, Swearer J, Hinerfeld D, Caselli R, Rogaeva E, St George-Hyslop P, Moonis M and Pollen DA: Long-term statin therapy and CSF cholesterol levels: Implications for Alzheimer's disease. Dement Geriatr Cogn Disord. 27:519–524. 2009. View Article : Google Scholar : PubMed/NCBI | |
Qin Z, Gu M, Zhou J, Zhang W, Zhao N, Lü Y and Yu W: Triggering receptor expressed on myeloid cells 2 activation downregulates toll-like receptor 4 expression and ameliorates cognitive impairment in the Aβ1-42-induced Alzheimer's disease mouse model. Synapse. 74:e221612020. View Article : Google Scholar | |
Price BR, Sudduth TL, Weekman EM, Johnson S, Hawthorne D, Woolums A and Wilcock DM: Therapeutic Trem2 activation ameliorates amyloid-beta deposition and improves cognition in the 5XFAD model of amyloid deposition. J Neuroinflammation. 17:2382020. View Article : Google Scholar : PubMed/NCBI | |
Fitz NF, Nam KN, Wolfe CM, Letronne F, Playso BE, Iordanova BE, Kozai TDY, Biedrzycki RJ, Kagan VE, Tyurina YY, et al: Phospholipids of APOE lipoproteins activate microglia in an Isoform-specific manner in preclinical models of Alzheimer's disease. Nat Commun. 12:34162021. View Article : Google Scholar : PubMed/NCBI | |
Griciuc A, Patel S, Federico AN, Choi SH, Innes BJ, Oram MK, Cereghetti G, McGinty D, Anselmo A, Sadreyev RI, et al: TREM2 Acts downstream of CD33 in modulating microglial pathology in Alzheimer's disease. Neuron. 103:820–835.e827. 2019. View Article : Google Scholar | |
Lefterov I, Schug J, Mounier A, Nam KN, Fitz NF and Koldamova R: RNA-sequencing reveals transcriptional up-regulation of Trem2 in response to bexarotene treatment. Neurobiol Dis. 82:132–140. 2015. View Article : Google Scholar : PubMed/NCBI | |
Tai LM, Koster KP, Luo J, Lee SH, Wang YT, Collins NC, Ben Aissa M, Thatcher GRJ and LaDu MJ: Amyloid-β pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo. J Biol Chem. 289:30538–30555. 2014. View Article : Google Scholar : | |
Khan N, Syed DN, Ahmad N and Mukhtar H: Fisetin: A dietary antioxidant for health promotion. Antioxid Redox Signal. 19:151–162. 2013. View Article : Google Scholar : | |
Prior M, Chiruta C, Currais A, Goldberg J, Ramsey J, Dargusch R, Maher PA and Schubert D: Back to the future with phenotypic screening. ACS Chem Neurosci. 5:503–513. 2014. View Article : Google Scholar | |
Ates G, Goldberg J, Currais A and Maher P: CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of Alzheimer's disease. Redox Biol. 36:1016482020. View Article : Google Scholar : PubMed/NCBI | |
Ayala A, Muñoz MF and Argüelles S: Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014:3604382014. View Article : Google Scholar : PubMed/NCBI | |
Oostveen JA, Dunn E, Carter DB and Hall ED: Neuroprotective efficacy and mechanisms of novel pyrrolopyrimidine lipid peroxidation inhibitors in the gerbil forebrain ischemia model. J Cereb Blood Flow Metab. 18:539–547. 1998. View Article : Google Scholar |