Open Access

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
  • View Affiliations

  • Published online on: July 8, 2025     https://doi.org/10.3892/ijmm.2025.5580
  • Article Number: 139
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and neuroinflammation, with microglial dysfunction emerging as a central driver of pathogenesis. Microglia, the central nervous system‑resident immune cells, exhibit dual pro‑inflammatory and anti‑inflammatory phenotypes, dynamically regulated by lipid metabolic reprogramming. Chronic activation of M1 microglia exacerbates neuronal damage, while M2 microglia promote tissue repair via phagocytic clearance and neurotrophic factor secretion. Lipid dysregulation‑marked by ceramide accumulation, cholesterol esterification defects and oxidized lipid‑driven neuroinflammation‑critically modulates microglial polarization. Mechanistic studies reveal that mitochondrial dysfunction, lysosomal stress and ferroptosis intersect with lipid metabolic pathways to amplify neurotoxicity. Therapeutic strategies targeting lipid homeostasis, such as TREM2 agonism, demonstrate efficacy in preclinical models by restoring microglial function and mitigating pathology. This review synthesizes emerging evidence linking microglial lipid metabolism to NDD progression, highlighting novel biomarkers and therapeutic avenues to disrupt the lipid‑neuroinflammation axis in neurodegeneration.
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September-2025
Volume 56 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Sun Y, Wei K, Liao X, Wang J, Gao L and Pang B: Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review). Int J Mol Med 56: 139, 2025.
APA
Sun, Y., Wei, K., Liao, X., Wang, J., Gao, L., & Pang, B. (2025). Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review). International Journal of Molecular Medicine, 56, 139. https://doi.org/10.3892/ijmm.2025.5580
MLA
Sun, Y., Wei, K., Liao, X., Wang, J., Gao, L., Pang, B."Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review)". International Journal of Molecular Medicine 56.3 (2025): 139.
Chicago
Sun, Y., Wei, K., Liao, X., Wang, J., Gao, L., Pang, B."Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review)". International Journal of Molecular Medicine 56, no. 3 (2025): 139. https://doi.org/10.3892/ijmm.2025.5580