Phenotypic manifestation of α-synuclein strains derived from Parkinson's disease and multiple system atrophy in human dopaminergic neurons.

ABSTRACT: α-Synuclein is critical in the pathogenesis of Parkinson's disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson's disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggere

SUBMITTER: Tanudjojo B 

PROVIDER: S-EPMC8217249 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature