Molecular chaperones and co-chaperones in parkinson disease

Hemi Dimant, Darius Ebrahimi-Fakhari, Pamela J. McLean

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations

Abstract

Parkinson disease, a progressive neurodegenerative disorder, is caused by the pathological accumulation of proteins, including the ubiquitous presynaptic protein α-synuclein. Alterations in the metabolism of α-synuclein have clearly been linked to neurodegeneration, and early steps in the pathological sequence of this protein include the formation of oligomers, fibrils, and small aggregates. Targeting these early steps of oligomerization is one of the main therapeutic approaches in the quest to develop disease-modifying agents. Molecular chaperones, molecules that can mediate the proper folding and refolding of client proteins, are vital to cell function and survival and thus have been explored as potential therapeutic agents. Important to Parkinson disease, chaperones are capable of preventing α-synuclein misfolding, oligomerization, and aggregate formation as shown in vitro and in Parkinson disease animal models. Furthermore, chaperones and associated co-chaperones are closely linked to pathways of protein degradation, like the ubiquitin-proteasome system and autophagy, and are thus able to remove irreversibly misfolded proteins. In this review, we summarize the role of molecular chaperones in Parkinson disease models and discuss the importance of preserving protein homeostasis to prevent neurodegeneration. We also review the growing number of exciting studies that have targeted molecular chaperone function as a novel therapeutic approach.

Original languageEnglish (US)
Pages (from-to)589-601
Number of pages13
JournalNeuroscientist
Volume18
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Parkinson disease
  • co-chaperone
  • heat shock protein (Hsp)
  • molecular chaperone
  • neurodegeneration
  • α-synuclein

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology

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