Lewy Body-like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α-Synuclein Mutations.

ABSTRACT:

Objective

We utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn- and Lewy body-related pathologies and the process of neurodegeneration in the hMLO model.

Methods

We generated and characterized hMLOs from GBA1^-/- and SNCA overexpressing isogenic embryonic stem cells and also generated Lewy body-like inclusions in GBA1/SNCA dual perturbation hMLOs and conduritol-b-epoxide-treated SNCA triplication hMLOs.

Results

We identified for the first time that the loss of glucocerebrosidase, coupled with wild-type α-syn overexpr

SUBMITTER: Jo J 

PROVIDER: S-EPMC9543721 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature