Lewy pathology formation in patient-derived GBA1 Parkinson's disease midbrain organoids.

ABSTRACT: Fibrillary aggregation of α-synuclein in Lewy body inclusions and nigrostriatal dopaminergic neuron degeneration define Parkinson's disease neuropathology. Mutations in GBA1, encoding glucocerebrosidase, are the most frequent genetic risk factor for Parkinson's disease. However, the lack of reliable experimental models able to reproduce key neuropathological signatures has hampered clarification of the link between mutant glucocerebrosidase and Parkinson's disease pathology. Here, we describe an innovative protocol for the generation of human induced pluripotent stem cell-derived midbrain organoids containing dopaminergic neurons with nigral identity that reproduce characteristics of advanced maturation. When applied to patients with GBA1-related Parkinson's disease, this method enabled th

SUBMITTER: Frattini E 

PROVIDER: S-EPMC11967528 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature