PAR2 activation increases α-synuclein expression, aggregation and phosphorylation in human oligodendrocytes with emphasis on pathophysiology of Multiple System Atrophy (MSA)

Abstract

The proteinase activated receptors (PARs) are a novel family of G protein–coupled receptors. Previous reports suggested the involvement of PAR2 signaling in neurodegenerative disorders. However, a role for PAR2 in Multiple System Atrophy, an adult onset sporadic neurodegenerative disease, has not been addressed. Aggregates of α-synuclein in the cytoplasm and in the nucleus of oligodendroctyes pathologically characterize this disease. I hypothesized that stimulation of PAR2 signaling increases α-synuclein expression, aggregation and phosphorylation. The results of current research show that stimulation of PAR2 receptor by three specific agonists, results in MAP Kinase (P42/44) phosphorylation and activation of the downstream pathways. Changes in α-synuclein monomer concentration and aggregation as well as phosphorylation in MO3.13 cells as the downstream effects of PAR2 activation can be correlated to MSA disease. These results may identify a potential therapeutic target upstream of α-synuclein aggregation and toxicity to prevent progression of multiple system atrophy.M.Sc.2020-11-15 00:00:0