Modelling α-Synuclein Aggregation and Neurodegeneration with Fibril Seeds in Primary Cultures of Mouse Dopaminergic Neurons.

ABSTRACT: To model α-Synuclein (αS) aggregation and neurodegeneration in Parkinson's disease (PD), we established cultures of mouse midbrain dopamine (DA) neurons and chronically exposed them to fibrils 91 (F91) generated from recombinant human αS. We found that F91 have an exquisite propensity to seed the aggregation of endogenous αS in DA neurons when compared to other neurons in midbrain cultures. Until two weeks post-exposure, somal aggregation in DA neurons increased with F91 concentrations (0.01-0.75 μM) and the time elapsed since the initiation of seeding, with, however, no evidence of DA cell loss within this time interval. Neither toxin-induced mitochondrial deficits nor genetically induced loss of mitochondrial quality control mechanisms promoted F91-mediated αS aggregation or neurodegener

SUBMITTER: Tourville A 

PROVIDER: S-EPMC9139621 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature