Waiting for PARIS-A Biological Target in Search of a Drug

J Parkinsons Dis. 2022;12(1):95-103. doi: 10.3233/JPD-212945.

Abstract

A recent breakthrough paper published in Science Translational Medicine has provided compelling evidence that inhibition of Parkin Interacting Substrate (PARIS) may offer clinical researchers an important new therapeutic approach since it shows considerable promise as an important biological target potentially capable of pharmaceutical intervention to slow long term neurodegeneration in patients with Parkinson's disease (PD). We present several PD-relevant perspectives on this paper that were not discussed in that otherwise entirely scientific narrative. We also outline the some of the work leading up to it, including the massive drug screen that proved necessary to discover a clinically suitable inhibitor of PARIS (Farnesol), as well as relevant PD research within the wider drug class, issues surrounding its future formulation, and next steps in translating this new knowledge into the clinic to evaluate possible long-term PD patient benefits.

Keywords: Farnesol; PARIS; PGC-1α; Parkin; iLCT; nanoformulation; neuroprotection.

MeSH terms

  • Dopaminergic Neurons*
  • Humans
  • Parkinson Disease* / drug therapy
  • Repressor Proteins
  • Ubiquitin-Protein Ligases

Substances

  • Repressor Proteins
  • Ubiquitin-Protein Ligases