In Parkinson's patient-derived dopamine neurons, the triplication of α-synuclein locus induces distinctive firing pattern by impeding D2 receptor autoinhibition.

ABSTRACT: Pathophysiological changes in dopamine neurons precede their demise and contribute to the early phases of Parkinson's disease (PD). Intracellular pathological inclusions of the protein α-synuclein within dopaminergic neurons are a cardinal feature of PD, but the mechanisms by which α-synuclein contributes to dopaminergic neuron vulnerability remain unknown. The inaccessibility to diseased tissue has been a limitation in studying progression of pathophysiology prior to degeneration of dopamine neurons. To address these issues, we differentiated induced pluripotent stem cells (iPSCs) from a PD patient carrying the α-synuclein triplication mutation (AST) and an unaffected first-degree relative (NAS) into dopaminergic neurons. In human-like dopamine neurons α-synuclein overexpression reduced t

SUBMITTER: Lin M 

PROVIDER: S-EPMC8185945 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature