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The autophagy-lysosomal pathway (ALP) is a critical intracellular protein degradation system responsible for maintaining proteostasis and metabolic balance within cells. Dysfunction of this pathway has been increasingly recognized as a key pathological basis underlying various neurodegenerative diseases (NDs). This review provides a comprehensive overview of the molecular mechanisms by which ALP impairment contributes to defective protein degradation in neurodegeneration. We focus on the impact of lysosomal structural integrity and functional imbalance on cellular fate, highlighting the interplay between protein oxidative damage and degradation system dysregulation. Furthermore, we summarize the current therapeutic strategies aimed at lysosomal repair, evaluating their potential clinical applications and efficacy. By integrating the latest research advances, this review aims to deepen the understanding of the pathological mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases, clarify the key molecular targets of lysosomal damage and repair, and provide theoretical basis for target screening and validation and practical reference for the development of targeted drugs for neurodegenerative diseases.
Wang et al. (Fri,) studied this question.