Small heat shock proteins protect against α-synuclein-induced toxicity and aggregation

Tiago Fleming Outeiro, Jochen Klucken, Katherine E. Strathearn, Fang Liu, Paul Nguyen, Jean Christophe Rochet, Bradley T. Hyman, Pamela J McLean

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Protein misfolding and inclusion formation are common events in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD) or Huntington's disease (HD). α-Synuclein (aSyn) is the main protein component of inclusions called Lewy bodies (LB) which are pathognomic of PD, Dementia with Lewy bodies (DLB), and other diseases collectively known as LB diseases. Heat shock proteins (HSPs) are one class of the cellular quality control system that mediate protein folding, remodeling, and even disaggregation. Here, we investigated the role of the small heat shock proteins Hsp27 and αB-crystallin, in LB diseases. We demonstrate, via quantitative PCR, that Hsp27 messenger RNA levels are ∼2-3-fold higher in DLB cases compared to control. We also show a corresponding increase in Hsp27 protein levels. Furthermore, we found that Hsp27 reduces aSyn-induced toxicity by ∼80% in a culture model while αB-crystallin reduces toxicity by ∼20%. In addition, intracellular inclusions were immunopositive for endogenous Hsp27, and overexpression of this protein reduced aSyn aggregation in a cell culture model.

Original languageEnglish (US)
Pages (from-to)631-638
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume351
Issue number3
DOIs
StatePublished - Dec 22 2006
Externally publishedYes

Fingerprint

Synucleins
Small Heat-Shock Proteins
Lewy Body Disease
Toxicity
Agglomeration
Crystallins
Parkinson Disease
Proteins
Lewy Bodies
Huntington Disease
Protein Folding
Heat-Shock Proteins
Neurodegenerative Diseases
Quality Control
Dementia
Alzheimer Disease
Neurodegenerative diseases
Cell Culture Techniques
Protein folding
Polymerase Chain Reaction

Keywords

  • α-Synuclein
  • Heat shock proteins
  • Lewy body
  • Neurodegenerative disease
  • Parkinson's disease
  • Protein misfolding

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Small heat shock proteins protect against α-synuclein-induced toxicity and aggregation. / Outeiro, Tiago Fleming; Klucken, Jochen; Strathearn, Katherine E.; Liu, Fang; Nguyen, Paul; Rochet, Jean Christophe; Hyman, Bradley T.; McLean, Pamela J.

In: Biochemical and Biophysical Research Communications, Vol. 351, No. 3, 22.12.2006, p. 631-638.

Research output: Contribution to journalArticle

Outeiro, Tiago Fleming ; Klucken, Jochen ; Strathearn, Katherine E. ; Liu, Fang ; Nguyen, Paul ; Rochet, Jean Christophe ; Hyman, Bradley T. ; McLean, Pamela J. / Small heat shock proteins protect against α-synuclein-induced toxicity and aggregation. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 351, No. 3. pp. 631-638.
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