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

Abstract

Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (alpha-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 alpha-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 alpha-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 alpha-syn aggregation. Furthermore, the PTMs modulating alpha-syn aggregation-induced cell death have been discussed.