The Life and Times of Brain Autophagic Vesicles

Journal of Molecular BiologyJournal of Molecular BiologyVolume 437, Issue 18, 15 September 2025, 169105Journal home page for Journal of Molecular BiologyAuthor links open overlay panel, , Highlights•

Not all the tools and methods used for monitoring autophagy are directly applicable to the brain.

Autophagy is implicated in key cognitive functions via its functions in diverse cellular contexts.

Neuronal autophagy is regulated by synaptic activity.

Non-canonical functions of autophagy are emerging in brain cells.

Abstract

Most of the knowledge on the mechanisms and functions of autophagy originates from studies in yeast and other cellular models. How this valuable information is translated to the brain, one of the most complex and evolving organs, has been intensely investigated. Fueled by the tight dependence of the mammalian brain on autophagy, and the strong links of human brain diseases with autophagy impairment, the field has revealed adaptations of the autophagic machinery to the physiology of neurons and glia, the highly specialized cell types of the brain. Here, we first provide a detailed account of the tools available for studying brain autophagy; we then focus on the recent advancements in understanding how autophagy is regulated in brain cells, and how it contributes to their homeostasis and integrated functions. Finally, we discuss novel insights and open questions that the new knowledge has raised in the field.

Graphical abstractDownload: Download high-res image (249KB)Download: Download full-size imageKeywords

brain

autophagic vesicles

homeostasis

synapse

selective autophagy

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© 2025 Published by Elsevier Ltd.

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