Modelling Parkinson’s disease in human dopaminergic neurons with α-synuclein and cytokines
October 2024
McGill University, Montreal, Canada
This study reveals that Lewy body (LB)-like inclusions, characteristic of Parkinson's disease (PD), can form in human dopaminergic neurons derived from induced pluripotent stem cells (iPSCs) under specific conditions. LB formation occurs when neurons are exposed to α-synuclein preformed fibrils (PFFs) combined with an immune challenge or co-culture with activated microglia-like cells. Interferon-γ exposure impairs lysosomal function, contributing to LB formation. Knockdown of LAMP2 or knockout of GBA genes, combined with PFF administration, is sufficient for inclusion formation. The LB-like inclusions are membrane-bound, suggesting they may result from autophagy dysfunction. These findings indicate that immune-triggered lysosomal dysfunction may play a role in PD pathology development.
Modeling Parkinson’s disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines
Peter S. McPherson, Armin Bayati
Added on: 12-03-2024
[1] https://www.nature.com/articles/s41593-024-01775-4[2] https://www.drugtargetreview.com/news/153590/new-link-found-between-immune-system-and-neurological-disease
