Endolysosomal and Autophagy Dysfunction in Neurodegenerative Diseases

Neurodegenerative disease research has increasingly focused on cellular degradation pathways, particularly the endolysosomal and autophagy systems, which are fundamental for neuronal health. Disorders such as Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and amyotrophic lateral sclerosis exhibit progressive neuronal loss alongside the pathological accumulation of toxic protein aggregates. A growing body of evidence reveals that impairments in lysosome acidification, enzyme functionality, organelle trafficking, and cargo degradation critically contribute to the disruption of neuronal proteostasis. Recent studies have elucidated the multifaceted nature of these dysfunctions, demonstrating their impact on neuroinflammation, synaptic health, and the overall resilience of neurons. Despite significant advances, major gaps remain in understanding the precise molecular mechanisms by which endolysosomal and autophagic failure drives neurodegeneration. There is an urgent need for deeper insight into cross-talk between these pathways, the regulation of organelle homeostasis, and the identification of key molecular defects that could serve as early biomarkers or therapeutic entry points.This Research Topic aims to provide a comprehensive synthesis of progress in elucidating endolysosomal and autophagy dysfunction in neurodegenerative diseases. By gathering multidisciplinary research, we seek to highlight novel mechanisms underlying lysosomal impairment, autophagosome processing defects, and abnormal organelle interactions. Our objective is to map the cascade of events connecting intracellular degradation failure to toxic protein accumulation, synaptic disturbance, inflammation, and neuronal dysfunction. Additionally, we aim to foster the identification and validation of promising biomarkers and therapeutic targets that could inform future strategies for disease intervention and prevention.The scope of this Research Topic is broad, encompassing all aspects of endolysosomal and autophagy pathway dysfunction in the context of neurodegeneration, while focusing specifically on mechanistic insights, pathophysiological consequences, and therapeutic innovation. We encourage submissions that use diverse models and methodologies, but exclude those not directly linked to intracellular degradation systems. To gather further insights in this dynamic area, we welcome articles addressing, but not limited to, the following themes:o Lysosomal enzyme activities and dysfunctiono Endosomal trafficking and its perturbationso Disruption of autophagic flux and maturationo Role of organelle acidification in neuronal healtho Impaired degradation and clearance of toxic protein aggregateso Synaptic vesicle recycling and related defectso Modulation of neuroinflammatory processes by degradation systemso Innovative therapeutic strategies targeting endolysosomal and autophagy functiono Development and application of biomarkers for early diagnosis and monitoring Topic editors: Chih Hung Lo, Fenghua Hu, Vidyadhara D J, Jialiu Zeng Source: https://www.frontiersin.org/research-topics/79017/endolysosomal-and-autophagy-dysfunction-in-neurodegenerative-diseases