Navigating the cellular pathways: Chaperone-mediated autophagy as a targeted approach for management of parkinson\'s disease

Authors : Pratiksha S Kawade, Shatrughna U Nagrik, Ganesh J Lamkhade, Ajay A Bhagwat, Rohit R Doke

DOI : 10.18231/j.jpbs.2023.005

Volume : 11

Issue : 1

Year : 2023

Page No : 26-29

Parkinson's disease (PD) is a common neurodegenerative condition marked by the degeneration of dopaminergic neurons and the amassing of ?-synuclein protein in Lewy bodies. Chaperone-mediated autophagy (CMA), a selective form of autophagy, has been implicated in the development of PD. Mutant GBA1, ?-synuclein, UCHL1, VPS35, and LRRK2 are affected proteins in PD that impair the CMA process. CMA Dysfunction cause accumulation of PD-associated proteins such as ?-synuclein and many other, including DJ-1, MEF2D, PARK7,etc resulting in mitochondrial dysfunctioning and apoptosis. The impact of gene mutations associated with PD on CMA has been observed, along with dysregulation of miRNAs targeting CMA components. Toxicant-induced PD models demonstrate that impaired CMA increases ?-synuclein aggregates and neurotoxicity. Understanding the molecular mechanisms of CMA has identified potential therapeutic targets, including increasing LAMP2A levels. Several compounds and substances have shown promise in enhancing CMA and reducing ?- synuclein aggregates, such as 6-aminonicotinamide, geldanamycin, metformin, and natural compounds like trehalose and caffeine. Pharmacological modulation of CMA, such as through retinoic acid derivatives, has demonstrated positive effects on reducing protein aggregates in neurodegenerative diseases. However, the specific effects of inhibiting CMA on macroautophagy remain uncertain. Overcoming challenges in studying CMA, such as developing suitable models and monitoring methods, is crucial for advancing our understanding of CMA's role in neurodegenerative diseases and developing effective therapeutic strategies. Overall, CMA emerges as a key player in the pathogenesis of PD, and targeting this selective autophagy pathway holds promise for developing novel therapies to combat neurodegenerative disorders.

Keywords: Autophagy, Chaperone, ­synuclein, LAMP2A, Chaperone­mediated autophagy ?

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