Molecular chaperones and co-chaperones in parkinson disease

Hemi Dimant, Darius Ebrahimi-Fakhari, Pamela J McLean

Research output: Contribution to journalArticle

31 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Molecular Chaperones
Synucleins
Parkinson Disease
Proteins
Protein Refolding
Autophagy
Proteasome Endopeptidase Complex
Ubiquitin
Neurodegenerative Diseases
Proteolysis
Cell Survival
Homeostasis
Therapeutics
Animal Models

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Molecular chaperones and co-chaperones in parkinson disease. / Dimant, Hemi; Ebrahimi-Fakhari, Darius; McLean, Pamela J.

In: Neuroscientist, Vol. 18, No. 6, 12.2012, p. 589-601.

Research output: Contribution to journalArticle

Dimant, Hemi ; Ebrahimi-Fakhari, Darius ; McLean, Pamela J. / Molecular chaperones and co-chaperones in parkinson disease. In: Neuroscientist. 2012 ; Vol. 18, No. 6. pp. 589-601.
@article{45c27fa3914344a1aa7b6a678ecc194e,
title = "Molecular chaperones and co-chaperones in parkinson disease",
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.",
keywords = "α-synuclein, co-chaperone, heat shock protein (Hsp), molecular chaperone, neurodegeneration, Parkinson disease",
author = "Hemi Dimant and Darius Ebrahimi-Fakhari and McLean, {Pamela J}",
year = "2012",
month = "12",
doi = "10.1177/1073858412441372",
language = "English (US)",
volume = "18",
pages = "589--601",
journal = "Neuroscientist",
issn = "1073-8584",
publisher = "SAGE Publications Inc.",
number = "6",

}

TY - JOUR

T1 - Molecular chaperones and co-chaperones in parkinson disease

AU - Dimant, Hemi

AU - Ebrahimi-Fakhari, Darius

AU - McLean, Pamela J

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

KW - α-synuclein

KW - co-chaperone

KW - heat shock protein (Hsp)

KW - molecular chaperone

KW - neurodegeneration

KW - Parkinson disease

UR - http://www.scopus.com/inward/record.url?scp=84865861347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865861347&partnerID=8YFLogxK

U2 - 10.1177/1073858412441372

DO - 10.1177/1073858412441372

M3 - Article

C2 - 22829394

AN - SCOPUS:84865861347

VL - 18

SP - 589

EP - 601

JO - Neuroscientist

JF - Neuroscientist

SN - 1073-8584

IS - 6

ER -