Role of post-translational modifications on the alpha-synuclein aggregation-related pathogenesis of Parkinson’s disease

• Published in: BMB reports 2022-07, Vol.55 (7), p.323-335
• Main Authors: Yoo, Hajung, Lee, Jeongmin, Kim, Bokwang, Moon, Heechang, Jeong, Huisu, Lee, Kyungmi, Song, Woo Jeung, Hur, Junho K, Oh, Yohan
• Format: Article
• Language: Korean
• Subjects: Alpha-synuclein; Parkinson’s disease; Post-translational modification; Protein aggregation
• ISSN: 1976-6696; 1976-670X

Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (α-syn) in the brain is widely accepted as a hallmark of synucleinopathies including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy body. Because the α-syn aggregates are deeply involved in the pathogenesis, there have been many attempts to demonstrate the mechanism of the aggregation and its potential causative factors including post-translational modifications (PTMs). Although no concrete conclusions have been made based on the previous study results, growing evidence suggests that modifications such as phosphorylation and ubiquitination can alter α-syn characteristics to have certain effects on the aggregation process in PD; either facilitating or inhibiting fibrillization. In the present work, we reviewed studies showing the significant impacts of PTMs on α-syn aggregation. Furthermore, the PTMs modulating α-syn aggregation-induced cell death have been discussed. [BMB Reports 2022; 55(7): 323-335]