The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson's disease.

The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson's disease. Acta Neurobiol Exp (Wars). 2019;79(3):276-289 Authors: Jęśko H, Lenkiewicz AM, Wilkaniec A, Adamczyk A Abstract Parkin and alpha-synuclein (α-syn) are two key proteins involved in the pathophysiology of Parkinson's disease (PD). Oligomerization/aggregation and excessive secretion of α-syn contributes to PD through free radical stress, mitochondrial impairment, and synaptic dysfunction. Parkin, an E3 ubiquitin ligase, is considered to be a pleiotropic, neuroprotective protein that modulates metabolic turnover and the accumulation of α-syn. This is in addition to parkin's role in counteracting the more distant effects of α-syn on cellular survival by altering proteasomal, autophagic, and calpain-mediated protein degradation pathways that can reduce α-syn levels. Moreover, parkin regulates mitochondrial turnover, cell survival, and immune phenomena - processes that are all known to be disturbed in PD. In addition, parkin might have an impact on the spreading and propagation of α-syn by controlling its post-translational modifications. On the other hand, recent research has shown that α-syn oligomers affect the expression, post-translational modification, and activity of parkin. This review focuses on the molecular mechanisms of cross-talk between parkin and α-syn in PD. The physical and functional interactions b...
Source: Acta Neurobiologiae Experimentalis - Category: Neurology Authors: Tags: Acta Neurobiol Exp (Wars) Source Type: research