ePoster

SHARING IS CARING - ASTROCYTES FACILITATE NEURONAL AUTOPHAGY

Katrin Lindaand 15 co-authors

Donders Institute for Brain, Cognition, and Behavior, Radboudumc

FENS Forum 2026 (2026)

Barcelona, Spain

Board PS04-08PM-199

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Board: PS04-08PM-199

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PS04-08PM-199

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Abstract

Autophagy is a catabolic process responsible for degradation of cytosolic components, and playing a key role in cellular homeostasis. At synapses, autophagy is crucial for regulating neuronal activity and utilizes a specialized machinery. While considerable progress has been made in understanding the initiation of autophagy and autophagosome formation, the mechanisms controlling their clearance from synaptic sites remain poorly understood. Here, we identify a novel pathway in which astrocytes actively participate in the clearance of pre-synaptic autophagosomes. Using neurons derived from human induced pluripotent stem cell-lines expressing fluorescent autophagy markers and chimeric mouse models, we demonstrate that neuronal autophagosomal vesicles are transferred to astrocytes, specifically when synaptic activity is suppressed. Autophagosome transfer does not require cellular contact, but it does require endocytosis for the internalized neuronal autophagosomes to ultimately fuse with astrocytic lysosomes. Our findings reveal a previously unrecognized mechanism of neuronal autophagosome clearance that bypasses retrograde axonal transport through astrocyte-mediated degradation.

SHARING IS CARING - ASTROCYTES FACILITATE NEURONAL AUTOPHAGY

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