Applying chaperones to protein-misfolding disorders: Molecular chaperones against α-synuclein in Parkinson's disease

Ali Chaari, Jessica Hoarau, Moncef Ladjimi

Research output: Contribution to journalReview article

27 Citations (Scopus)

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of a protein called α-synuclein (α-syn) into inclusions known as lewy bodies (LB) within neurons. This accumulation is also due to insufficient formation and activity of dopamine produced in certain neurons within the substantia nigra. Lewy bodies are the pathological hallmark of the idiopathic disorder and the cascade that allows α-synuclein to misfold, aggregate and form these inclusions has been the subject of intensive research. Targeting these early steps of oligomerization is one of the main therapeutic approaches in order to develop neurodegenerative-modifying agents. Because the folding and refolding of alpha synuclein is the key point of this cascade, we are interested in this review to summarize the role of some molecular chaperones proteins such as Hsp70, Hsp90 and small heat shock proteins (sHsp) and Hsp 104. Hsp70 and its co-chaperone, Hsp70 and small heat shock proteins can prevent neurodegeneration by preventing α-syn misfolding, oligomerization and aggregation in vitro and in Parkinson disease animal models. Hsp104 is able to resolve disordered protein aggregates and cross beta amyloid conformers. Together, these chaperones have a complementary effect and can be a target for therapeutic intervention in PD.

Original languageEnglish
Pages (from-to)196-205
Number of pages10
JournalInternational Journal of Biological Macromolecules
Volume60
DOIs
Publication statusPublished - 1 Sep 2013

Fingerprint

Proteostasis Deficiencies
Synucleins
Molecular Chaperones
Small Heat-Shock Proteins
Parkinson Disease
Lewy Bodies
Oligomerization
Neurons
alpha-Synuclein
Proteins
Substantia Nigra
Amyloid
Neurodegenerative Diseases
Dopamine
Animals
Agglomeration
Animal Models
Therapeutics
Research

Keywords

  • α-synuclein
  • Aggregation
  • Molecular chaperones
  • Parkinson's disease
  • Refolding

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Applying chaperones to protein-misfolding disorders : Molecular chaperones against α-synuclein in Parkinson's disease. / Chaari, Ali; Hoarau, Jessica; Ladjimi, Moncef.

In: International Journal of Biological Macromolecules, Vol. 60, 01.09.2013, p. 196-205.

Research output: Contribution to journalReview article

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