The role of glia autophagy in CNS homeostasis, ageing and disease

Le résumé fourni par la source

Autophagy is a fundamental catabolic process that is critical for maintaining cellular homeostasis and protein quality control in the central nervous system (CNS). While neuronal autophagy has been extensively characterized, growing evidence highlights the indispensable roles of glial autophagy, specifically in astrocytes, oligodendrocytes and microglia, in CNS physiology and pathology. These glial populations employ the autophagic machinery to regulate distinct but interconnected functions: astrocytes manage metabolic support and glutamate homeostasis; oligodendrocytes rely on autophagic flux for differentiation and myelin maintenance; and microglia employ specific pathways, such as LC3-associated phagocytosis, to orchestrate immune surveillance and inflammasome regulation. Impairment of glial autophagy has been implicated in non-cell-autonomous neurodegeneration, leading to excitotoxicity, myelin damage, the emergence of senescence-associated secretory phenotypes, and persistent neuroinflammation. Dysregulation of autophagic pathways during ageing has also been implicated in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. In this review we summarize the cell-type-specific molecular mechanisms of autophagy in glia, and delineate their role in the clearance of pathogenic aggregates such as β-amyloid, α-synuclein, and mutant huntingtin. A deeper understanding of the spatiotemporal dynamics of glial autophagy and associated intercellular crosstalk is essential to fully elucidate the complex etiology of age-associated neurodegenerative conditions.

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