Objective: The research how to better understand the molecular mechanism initiating the etiology of Parkinson’s disease in order to appropriate the precise diagnosis and therapeutic approach to the neurodegenerative disease.

Background: Impairment of autophagy-lysosomal pathways (ALPs) is considered a significant pathogenic event in neurodegenerative disorders, including Parkinson’s disease (PD).

ALP modifications are seen in sporadic PD brains and in toxic and genetic rodent models of PD-associated neurodegeneration.

Moreover, PD-associated mutations and post-translational modifications of α-synuclein hinder its own lysosomal-mediated degradation, thus contributing to its buildup and aggregation.

Method: The research took into deep search of literatures articulated in the understanding of Parkinson’s disease, alpha synuclein biopathology and dysregulation of cellular protein metabolism.

Results: Impairment of autophagy-lysosomal pathways (ALPs) is  regarded as a major pathogenic event in neurodegenerative diseases, including Parkinson’s disease (PD). 

ALP alterations are observed in sporadic PD brains and in toxic and genetic rodent models of PD-related neurodegeneration. 

In addition, PD-linked mutations and post-translational modifications of α-synuclein impair its own lysosomal-mediated degradation, thereby contributing to its accumulation and aggregation. 

Furthermore, other PD-related genes, such as leucine-rich repeat kinase-2 (LRRK2), parkin, and phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), have been mechanistically linked to alterations in ALPs.

Conclusion: In Parkinson’s disease, the autosomal lysosomal system plays a critical role as its dysfunction, particularly in the degradation of alpha-synuclein protein, is considered a key pathogenic mechanism, with several genes linked to Parkinson’s directly impacting lysosomal function, leading to protein aggregation and neuronal damage; essentially, mutations in these genes disrupt the normal process of cellular waste disposal within the lysosome, contributing to the disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-autophagy-lysosomal-and-ubiquitin-proteasomal-system-in-the-pathophysiology-of-parkinsons-disease/