Lipophagy and lipid droplets in neurodegeneration.

Authors

Nicholas W McKee, Yue Jing, Rashid Serdah, Senthilkumar Thulasingam, Xenia S Lopez, Ee Phie Tan

Published in

Trends in pharmacological sciences. Sep 22, 2026. Epub Sep 22, 2026.

Abstract

Lipid droplet (LD) accumulation in neurons and glia is a feature of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) and is associated with oxidative stress and neuroinflammation. Although protein-targeted monotherapies have achieved partial clinical success, continued disease progression in many patients suggests that additional cellular mechanisms contribute to pathogenesis. Lipophagy, the selective autophagic degradation of LDs, provides a potential clearance route but has been studied primarily in hepatocytes under nutrient deprivation. Recent studies have begun to map noncanonical regulatory mechanisms of lipophagy, identify disease-associated points of failure in AD, PD, and ALS, and report compounds that enhance LD clearance through mechanisms distinct from canonical nutrient sensing. In this article, we review these advances and discuss the emerging rationale for exploring neuron- and context-specific approaches to modulate lipophagy as a complementary strategy in neurodegeneration.

PMID:
42773049
Bibliographic data and abstract were imported from PubMed on 23 Sep 2026.

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