Neurodegenerative disorders, including Alzheimer's disease (AD), Frontotemporal dementia (FTD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal loss and accumulation of toxic protein aggregates. Emerging evidence highlights dysfunction in the endolysosomal and autophagy pathways as key contributors to disease pathogenesis. These intracellular degradation systems play essential roles in organelle acidification, enzyme activation, clearance of damaged cellular components, and regulation of neuroinflammation and neuronal functions. Deficiencies in lysosomal acidification, enzyme activities, impaired fusion of endosomes and autophagosomes with lysosomes, and defective protein degradation mechanisms disrupt cellular homeostasis and exacerbate neuroinflammation and neuronal vulnerability. Understanding the molecular underpinnings of these dysfunctions is crucial for developing effective therapeutic strategies aimed at restoring proteostasis and preventing neurodegeneration.

This Research Topic aims to provide a comprehensive overview of recent advancements in understanding the role of endolysosomal and autophagy dysfunction in neurodegenerative diseases. We seek to highlight novel insights into mechanisms underlying lysosomal impairment, defective autophagosome maturation, and disrupted organelle trafficking. Furthermore, the Research Topic will explore how these dysfunctions contribute to disease pathology, including toxic protein accumulation, synaptic dysfunction, neuroinflammatory responses, and neuronal impairments. By bringing together cutting-edge research, we aim to identify potential biomarkers and therapeutic targets that could lead to novel interventions for neurodegenerative disorders.

We invite original research articles, reviews, and perspectives that address critical aspects of endolysosomal and autophagy dysfunction in neurodegeneration. Topics of interest include, but are not limited to:

o Lysosomal enzyme activities

o Endosomal trafficking defects

o Autophagic flux disruption

o The role of organelle acidification in cellular functions

o The impact of impaired degradation of toxic protein aggregates

o Synaptic vesicle recycling defects

Additionally, we welcome studies exploring innovative therapeutic strategies aimed at restoring endolysosomal function and enhancing autophagic clearance. By contributing to this collection, authors will have the opportunity to present pioneering work that advances our understanding of neurodegenerative disease mechanisms and informs future therapeutic development.

Are you interested in contributing a manuscript to this Research Topic?

Endolysosomal and autophagy dysfunction in neurodegenerative diseases