Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein.

ABSTRACT: Parkinson's disease is a progressive neurodegenerative disorder characterised by the accumulation of misfolded α-synuclein in selected brain regions, including the substantia nigra pars compacta (SNpc), where marked loss of dopaminergic neurons is also observed. Yet, the relationship between misfolded α-synuclein and neurotoxicity currently remains unclear. As the principal route for degradation of misfolded proteins in mammalian cells, the ubiquitin-proteasome system (UPS) is critical for maintenance of cellular proteostasis. Misfolded α-synuclein impairs UPS function and contributes to neuronal death in vitro. Here, we examine its effects in vivo using adeno-associated viruses to co-express A53T α-synuclein and the ubiquitinated reporter protein Ub^G76V-GFP in rat SNpc. We foun

SUBMITTER: McKinnon C 

PROVIDER: S-EPMC7023783 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature