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

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초록

Together with neuronal loss, the existence of insoluble inclusionsof alpha-synuclein (α-syn) in the brain is widely acceptedas a hallmark of synucleinopathies including Parkinson’s disease(PD), multiple system atrophy, and dementia with Lewybody. Because the α-syn aggregates are deeply involved in thepathogenesis, there have been many attempts to demonstratethe mechanism of the aggregation and its potential causativefactors including post-translational modifications (PTMs). Althoughno concrete conclusions have been made based on theprevious study results, growing evidence suggests that modificationssuch as phosphorylation and ubiquitination can alterα-syn characteristics to have certain effects on the aggregationprocess in PD; either facilitating or inhibiting fibrillization. Inthe present work, we reviewed studies showing the significantimpacts of PTMs on α-syn aggregation. Furthermore, the PTMsmodulating α-syn aggregation-induced cell death have beendiscussed.

Abstract

Together with neuronal loss, the existence of insoluble inclusionsof alpha-synuclein (α-syn) in the brain is widely acceptedas a hallmark of synucleinopathies including Parkinson’s disease(PD), multiple system atrophy, and dementia with Lewybody. Because the α-syn aggregates are deeply involved in thepathogenesis, there have been many attempts to demonstratethe mechanism of the aggregation and its potential causativefactors including post-translational modifications (PTMs). Althoughno concrete conclusions have been made based on theprevious study results, growing evidence suggests that modificationssuch as phosphorylation and ubiquitination can alterα-syn characteristics to have certain effects on the aggregationprocess in PD; either facilitating or inhibiting fibrillization. Inthe present work, we reviewed studies showing the significantimpacts of PTMs on α-syn aggregation. Furthermore, the PTMsmodulating α-syn aggregation-induced cell death have beendiscussed.

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