Molecular chaperones in Parkinson's disease - Present and future

Darius Ebrahimi-Fakhari, Lara Wahlster, Pamela J McLean

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Parkinson's disease, like many other neurodegenerative disorders, is characterized by the progressive accumulation of pathogenic protein species and the formation of intracellular inclusion bodies. The cascade by which the small synaptic protein α-synuclein misfolds to form distinctive protein aggregates, termed Lewy bodies and Lewy neurites, has been the subject of intensive research for more than a decade. Genetic and pathological studies in Parkinson's disease patients as well as experimental studies in disease models have clearly established altered protein metabolism as a key element in the pathogenesis of Parkinson's disease. Alterations in protein metabolism include misfolding and aggregation, post-translational modification and dysfunctional degradation of cytotoxic protein species. Protein folding and re-folding are both mediated by a highly conserved network of molecules, called molecular chaperones and co-chaperones. In addition to the regulatory role in protein folding, molecular chaperone function is intimately associated with pathways of protein degradation, such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway, to effectively remove irreversibly misfolded proteins. Because of the central role of molecular chaperones in maintaining protein homeostasis, we herein review our current knowledge on the involvement of molecular chaperones and co-chaperones in Parkinson's disease. We further discuss the capacity of molecular chaperones to prevent or modulate neurodegeneration, an important concept for future neuroprotective strategies and summarize the current progress in preclinical studies in models of Parkinson's disease and other neurodegenerative disorders. Finally we include a discussion on the future potential of using molecular chaperones as a disease modifying therapy.

Original languageEnglish (US)
Pages (from-to)299-320
Number of pages22
JournalJournal of Parkinson's Disease
Volume1
Issue number4
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Molecular Chaperones
Parkinson Disease
Proteins
Protein Folding
Neurodegenerative Diseases
Proteolysis
Synucleins
Lewy Bodies
Inclusion Bodies
Autophagy
Neurites
Proteasome Endopeptidase Complex
Post Translational Protein Processing
Ubiquitin
Homeostasis
Research

Keywords

  • alpha-synuclein
  • autophagy
  • heat shock protein (Hsp)
  • Hsp90 inhibitor
  • Lewy body
  • lysosome
  • molecular chaperone
  • Neurodegeneration
  • Parkinson's disease
  • proteasome

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Molecular chaperones in Parkinson's disease - Present and future. / Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J.

In: Journal of Parkinson's Disease, Vol. 1, No. 4, 2011, p. 299-320.

Research output: Contribution to journalArticle

Ebrahimi-Fakhari, Darius ; Wahlster, Lara ; McLean, Pamela J. / Molecular chaperones in Parkinson's disease - Present and future. In: Journal of Parkinson's Disease. 2011 ; Vol. 1, No. 4. pp. 299-320.
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