Systemic α-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is an α-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including α-synuclein preformed fibrils (pff). We show that a single systemic administration of α-synuclein pff triggers pathological transformation of endogenous α-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The α-synuclein pathology generated was both time dependent and region specific. Interestingly,

SUBMITTER: Kuan WL 

PROVIDER: S-EPMC7850975 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature