Targeting heat shock proteins to modulate α-synuclein toxicity

Daryl Rhys Jones, Simon Moussaud, Pamela J McLean

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 - 2014

Fingerprint

Synucleins
Heat-Shock Proteins
Parkinson Disease
Protein Refolding
Therapeutics
Hypokinesia
Molecular Chaperones
Dopaminergic Neurons
Protein Folding
Neurodegenerative Diseases
Proteolysis
Animal Models
Research Personnel
Pharmacology

Keywords

  • α-synuclein
  • heat shock protein
  • molecular chaperones
  • parkinsonism

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Pharmacology

Cite this

Targeting heat shock proteins to modulate α-synuclein toxicity. / Jones, Daryl Rhys; Moussaud, Simon; McLean, Pamela J.

In: Therapeutic Advances in Neurological Disorders, Vol. 7, No. 1, 2014, p. 33-51.

Research output: Contribution to journalArticle

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