Loss of the lysosomal lipid flippase ATP10B leads to progressive dopaminergic neurodegeneration and parkinsonian motor deficits.

ABSTRACT: ATP10B, a transmembrane lipid flippase located in late endosomes and lysosomes, facilitates the export of glucosylceramide and phosphatidylcholine by coupling this process to ATP hydrolysis. Recently, loss-of-function mutations in the ATP10B gene have been identified in Parkinson's disease patients, pointing to ATP10B as a candidate genetic risk factor. Previous studies have shown compromised lysosomal functionality upon ATP10B knockdown in human cell lines and primary cortical neurons. To investigate the role of ATP10B in Parkinson's disease neuropathology, specifically in the nigrostriatal dopaminergic system, we induced ATP10B knockdown specifically in substantia nigra pars compacta neurons of rats using viral vector technology. Additionally, midbrain neuronal cultures derived from ATP1

SUBMITTER: Sanchiz-Calvo M 

PROVIDER: S-EPMC12271281 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature