Functional validation of a human GLUD2 variant in a murine model of Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GL

SUBMITTER: Zhang W 

PROVIDER: S-EPMC7582183 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature