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Decoy Molecule Blocks Alpha‑Synuclein–ClpP Link, Reversing Mitochondrial Defects in Parkinson’s Models

Preclinical data point to a harmful protein interaction with a candidate that restores cellular energy systems.

Overview

  • Case Western Reserve researchers identified aberrant binding between alpha‑synuclein and the mitochondrial enzyme ClpP that undermines neuronal health.
  • The team designed a decoy compound, CS2, to divert alpha‑synuclein from ClpP and restore mitochondrial function.
  • Across human brain tissue, patient‑derived neurons, and mouse models, CS2 improved movement and cognitive measures while reducing brain inflammation.
  • The findings were published in Molecular Neurodegeneration in 2025 (DOI: 10.1186/s13024-025-00918-w).
  • Researchers are now optimizing the candidate and planning safety, efficacy, and biomarker studies toward possible clinical trials within roughly five years.