Targeting the ClpP-αSynuclein Interaction with a Decoy Peptide to Mitigate Neuropathology in Parkinson's Disease Models.

ABSTRACT: Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic (DA) neurons and the accumulation of α-synuclein (αSyn)-rich inclusions. Despite advances in understanding PD pathophysiology, disease-modifying therapies remain elusive, underscoring gaps in our knowledge of its underlying mechanisms. Mitochondria are key targets of αSyn toxicity, and growing evidence suggests that αSyn-mitochondrial interactions contribute to PD progression. Our recent findings identify mitochondrial protease ClpP as a crucial regulator of αSyn pathology, with pathological αSyn binding to and impairing ClpP function, thereby exacerbating mitochondrial impairment and neurodegeneration. To disrupt this deleterious interaction, we develo

SUBMITTER: Hu D 

PROVIDER: S-EPMC11870492 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature