Du T, Wu Z, Luo H, Lu S, Ma K

Pathological aggregation of ?-synuclein (?-syn) is a major component of Lewy bodies (LB), which play a central role in pathogenesis of Parkinson's disease (PD). Differential expression of ?-syn isoforms has been shown in PD. Isoform ?-syn-98 is generated by excision of exon-3 and exon-5 of the ?-syn gene. In contrast ...

Read More

to the canonical full-length ?-syn isoform (?-syn140), little is known about the function of the ?-syn-98 isoform. In the present study, to identify the potential role of ?-syn-98 protein in PD, we examined the effects of exogenous recombinant insoluble ?-syn-98 aggregates on ?-syn pathology and inflammatory responses in the midbrain. After injection of ?-syn-98 aggregates into the substantia nigra (SN), mice exhibited motor dysfunction accompanied by nigral dopaminergic neuron loss. In addition, ?-syn-98 aggregates injection resulted in a significant increase in phosphorylation of endogenous ?-syn. Accumulations of ?-syn were co-localized with p62 and ubiquitin, which suggests ?-syn-98 aggregates-induced pathology exhibits properties similar to human LB. Many glial cells were activated after ?-syn-98 aggregates injection. In addition, expression of NF-?B, interleukin 6 (IL6), and tumor necrosis factor-? (TNF-?) and levels of oxidative stress increased after ?-syn-98 aggregates injection. Our results suggest that ?-syn-98 may play a crucial role in the pathogenesis of PD.

Date: Aug. 27, 2019

View in: Pubmed Google Scholar

222344