Molecular chaperones and Parkinson's disease.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive death of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies (LBs). Mutations in PD-related genes lead to neuronal pathogenesis through various mechanisms, with known examples including SNCA/α-synuclein (PAKR1), Parkin (PARK2), PINK1 (PARK6), DJ-1 (PARK7), and LRRK2 (PARK8). Molecular chaperones/co-chaperones are proteins that aid the folding of other proteins into a functionally active conformation. It has been demonstrated that chaperones/co-chaperones interact with PD-related proteins and regulate their function in PD. HSP70, HSP90 and small heat shock proteins can prevent neurodegeneration by regulating α-syn misfolding, oligomerization and aggregation. The function of chaperones is regulated by co-chaperones such as HSP110, HSP40, HOP, CHIP, and BAG family proteins. Parkin, PINK1 and DJ-1 are PD-related proteins which are associated with mitochondrial function. Molecular chaperones regulate mitochondrial function and protein homeostasis by interacting with these PD-related proteins. This review discusses critical molecular chaperones/co-chaperones and PD-related proteins which contribute to the pathogenesis of PD, hoping to provide new molecular targets for therapeutic interventions to thwart the disease progression instead of only bringing symptomatic relief. Moreover, appreciating the critical role of chaperones in PD can also help us screen efficient biomarkers to identify PD at an early stage.

• Authors: Shenglan Hu, Jieqiong Tan, Lixia Qin, Lingling Lv, Weiqian Yan, Hainan Zhang, BeiSha Tang, Chunyu Wang
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 160 Pg. 105527 (12 2021) ISSN: 1095-953X [Electronic] United States
• PMID: 34626793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Molecular Chaperones
• alpha-Synuclein
• Ubiquitin-Protein Ligases
• parkin protein

Topics

• Animals
• Disease Models, Animal
• Dopaminergic Neurons (metabolism, pathology)
• Humans
• Molecular Chaperones (metabolism)
• Parkinson Disease (metabolism, pathology)
• Substantia Nigra (metabolism, pathology)
• Ubiquitin-Protein Ligases (metabolism)
• alpha-Synuclein (metabolism)