GHSR deficiency exacerbates Parkinson's disease pathology by impairing autophagy.

ABSTRACT: In Parkinson's disease (PD), exogenous ghrelin protects dopaminergic neurons through its receptor, growth hormone secretagogue receptor (GHSR). However, in contrast to the strikingly low levels of ghrelin, GHSR is highly expressed in the substantia nigra (SN). What role does GHSR play in dopaminergic neurons is unknown. In this study, using GHSR knockout mice (Ghsr^-/- mice) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, we found that GHSR deletion aggravated dopaminergic neurons degeneration, and the expression and activity of GHSR were significantly reduced in PD. Furthermore, we explored the potential mechanism that GHSR deficiency aggregated PD-related neurodegeneration. We showed that DEPTOR, a subunit of mTORC1, was overexpressed in Ghsr^-/-</

SUBMITTER: Xiao X 

PROVIDER: S-EPMC11388265 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature