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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

153 Citations (Scopus)


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
Pages (from-to)631-638
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 22 Dec 2006
Externally publishedYes


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


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