Next questions of autophagy in neurodegenerative diseases: From mechanisms to therapeutics

Autophagy, a key cellular degradation pathway, is central to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Despite progress in understanding its role, critical questions remain. This perspective highlights pressing issues, including cell-type-specific autophagy regulation, interactions with other cellular pathways, and challenges in translating autophagy-modulating therapies to clinical practice. Addressing these questions will advance our understanding of neurodegenerative diseases and pave the way for novel therapeutics.

Introduction

Neurodegenerative diseases are characterized by progressive neuronal loss and toxic protein aggregate accumulation. Autophagy, a critical cellular degradation pathway, plays a central role in these disorders. However, several key questions remain unanswered. This perspective aims to address these questions, focusing on cell-type-specific autophagy regulation, interactions with other cellular pathways, and challenges in translating autophagy-modulating therapies to clinical practice. Recent studies have highlighted the dual roles of autophagy in promoting and inhibiting inflammation in microglia, emphasizing the need for a nuanced understanding of these mechanisms.