Nigral ATP13A2 depletion induces Parkinson's disease-related neurodegeneration in a pilot study in non-human primates.

ABSTRACT: Lysosomal impairment is strongly implicated in Parkinson's disease (PD). Among the several PD-linked genes, the ATP13A2 gene, associated with the PARK9 locus, encodes a transmembrane lysosomal P5-type ATPase. Mutations in the ATP13A2 gene were primarily identified as the cause of Kufor-Rakeb syndrome (KRS), a juvenile-onset form of PD. Subsequently, an increasing list of several mutations has been described. These mutations result in truncation of the ATP13A2 protein, leading to a loss of function but surprisingly causing heterogeneity and variability in the clinical symptoms associated with different brain pathologies. In vitro studies show that its loss compromises lysosomal function, contributing to cell death. To understand the role of ATP13A2 dysfunction in disease, we disrupted its e

SUBMITTER: Sikora J 

PROVIDER: S-EPMC11294619 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature