Lipid Droplet-Accumulating Microglia as a Therapeutic Node in Neurodegenerative Disease.

Siqi Guo, Qingyu Zhang, Rui Guo, Liyuan Fu, Huaxu Zhu, Qichun Zhang

Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. · pubmed

Paper

Abstract

Neurodegenerative disorders increasingly reflect failures of cellular state control rather than the linear accumulation of a single toxic lesion. Microglia become trapped in maladaptive states in which inflammatory activation is decoupled from effective cargo processing. Lipid droplet-accumulating microglia (LDAM) represent a recurrent convergence state across aging and neurodegeneration, characterized by persistent neutral lipid sequestration, reduced phagocytosis-to-degradation capacity, oxidative amplification, and chronic but functionally inefficient inflammation. LDAM emerges when lipid substrate influx exceeds the capacity of cholesterol efflux, lysosomal lipophagy, and mitochondrial β-oxidation, converting lipid droplets from transient buffers into stable metabolic anchors. This entrenchment is reinforced by mitochondrial exhaustion, vacuolar H

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Research summary

The paper claims that lipid droplet-accumulating microglia represent a maladaptive state in neurodegenerative diseases that could be targeted for therapeutic intervention. This research is relevant as it addresses the underlying mechanisms of cellular dysfunction in aging and neurodegeneration, potentially offering insights into the root causes of age-related diseases.

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