Targeting heat shock proteins to modulate α-synuclein toxicity

Daryl Rhys Jones, Simon Moussaud, Pamela Mclean

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

Parkinson's disease is a slowly progressive neurodegenerative disorder typically characterized by the loss of dopaminergic neurons within the substantia nigra pars compacta, and the intraneuronal deposition of insoluble protein aggregates chiefly comprised of α-synuclein. Patients experience debilitating symptoms including bradykinesia, rigidity and postural instability. No curative treatment currently exists and therapeutic strategies are restricted to symptomatic treatment only. Over the past decade a class of molecular chaperones called the heat shock proteins has emerged as a potentially promising therapeutic target. Heat shock proteins aid in the folding and refolding of proteins, and target denatured proteins to degradation systems. By targeting heat shock proteins through various means including overexpression and pharmacological enhancement, researchers have shown that α-synuclein aggregation and its associated cytotoxicity can be therapeutically modulated in an array of cell and animal models. This review highlights the relevant progress in this field and discusses the relevance of heat shock proteins as therapeutic modulators of α-synuclein toxicity to the rapidly evolving understanding of Parkinson's disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)33-51
Number of pages19
JournalTherapeutic Advances in Neurological Disorders
Volume7
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • heat shock protein
  • molecular chaperones
  • parkinsonism
  • αsynuclein

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Targeting heat shock proteins to modulate α-synuclein toxicity'. Together they form a unique fingerprint.

  • Cite this