MCL1 as a Therapeutic Target in Parkinson's Disease?

Trends Mol Med. 2019 Dec;25(12):1056-1065. doi: 10.1016/j.molmed.2019.08.009. Epub 2019 Nov 6.

Abstract

Dopamine neurons in the substantia nigra (SN) pars compacta are selectively lost during the progression of Parkinson's disease (PD). Recent work performed on the role of the Bcl2 family (highly specialized proteins which control cellular survival and death) in midbrain dopamine neurons has led to the identification of the Bcl2 factor Mcl1 as a weak link in the survival of these neurons. We hypothesize that the regulation of BCL2 proteins may explain this selective vulnerability, and may even provide a novel therapeutic opportunity - strengthening weak links such as MCL1 could result in a delay or complete abrogation of cell death during PD.

Keywords: Bcl2; apoptosis; cell death; dopamine; mitochondria; neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Humans
  • Molecular Targeted Therapy
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Peptides / pharmacology
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Small Molecule Libraries / pharmacology
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Ubiquitin / metabolism

Substances

  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Peptides
  • Proto-Oncogene Proteins c-bcl-2
  • Small Molecule Libraries
  • Ubiquitin
  • Proteasome Endopeptidase Complex