Disrupting α-Synuclein-ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson's disease models.

ABSTRACT:

Background

Mitochondrial dysfunction and α-Synuclein (αSyn) aggregation are defining features of Parkinson's disease (PD), yet the mechanistic link between them remains poorly understood. Although our previous findings suggest that the interaction between αSyn and ClpP (a mitochondrial matrix protease) contributes to PD progression, the pathogenic and therapeutic relevance of this interaction remains elusive.

Methods

We employed biochemical and cell biological approaches to investigate how αSyn and ClpP are mutually regulated. Additionally, we determined the pathogenic impact of αSyn-ClpP interaction by using decoy peptide CS2 in αSyn-PFF inoculated primary neurons, PD patient iPSC-derived dopaminergic neurons, and a transgenic mouse model of PD carrying αSyn-A53T mutation.<

SUBMITTER: Hu D 

PROVIDER: S-EPMC12751141 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature