Autophagy intersection: Unraveling the role of the SNARE complex in lysosomal fusion in Alzheimer's disease.

Abstract

Autophagy is a fundamental cellular process critical for maintaining neuronal health, particularly in the context of neurodegenerative diseases such as Alzheimer's disease (AD). This review explores the intricate role of the SNARE complex in the fusion of autophagosomes with lysosomes, a crucial step in autophagic flux. Disruptions in this fusion process, often resulting from aberrant SNARE complex function or impaired lysosomal acidification, contribute to the pathological accumulation of autophagosomes and lysosomes observed in AD. We examine the composition, regulation, and interacting molecules of the SNARE complex, emphasizing its central role in autophagosome-lysosome fusion. Furthermore, we discuss the potential impact of specific SNARE protein mutations and the broader implications for neuronal health and disease progression. By elucidating the molecular mechanisms underlying SNARE-mediated autophagic fusion, we aim to highlight therapeutic targets that could restore autophagic function and mitigate the neurodegenerative processes characteristic of AD.