Inhibiting TRPV4 improves α-synuclein degradation through autophagy-lysosomal pathway in the MPP⁺-induced cell model of parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is a prevalent neurodegenerative disorder often accompanied by dementia in its advanced stages. The pathogenesis of PD dementia involves abnormal autophagy and the accumulation of phosphorylated at serine 129 α-synuclein (pS129 α-syn). Proper functioning of the autophagy-lysosomal pathway (ALP) is essential for the effective degradation of pS129 α-syn. Our previous studies implicated the calcium channel transient receptor potential vanilloid 4 (TRPV4) in dopaminergic neuron degeneration by demonstrating that its overexpression induces endoplasmic reticulum stress and inflammation, driving neuronal loss-a hallmark of PD. This study aimed to investigate the role of TRPV4 in ALP-mediated pS129 α-syn clearance in the 1-methyl-4-phenylpyridinium ion (MPP⁺)-in

SUBMITTER: Bai Y 

PROVIDER: S-EPMC12660967 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature