Small heat shock proteins protect against {alpha}-synuclein-induced toxicity and aggregation

• Published in: Biochemical and biophysical research communications 2006-12, Vol.351 (3)
• Main Authors: Outeiro, Tiago Fleming, Klucken, Jochen, Strathearn, Katherine E., Liu Fang, Nguyen, Paul, Rochet, Jean-Christophe, Hyman, Bradley T., McLean, Pamela J.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; AGGLOMERATION; CELL CULTURES; HEAT-SHOCK PROTEINS; MESSENGER-RNA; NERVOUS SYSTEM DISEASES; POLYMERASE CHAIN REACTION; QUALITY CONTROL; TOXICITY
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.10.085

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). {alpha}-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 {alpha}B-crystallin, in LB diseases. We demonstrate, via quantitative PCR, that Hsp27 messenger RNA levels are {approx}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 {approx}80% in a culture model while {alpha}B-crystallin reduces toxicity by {approx}20%. In addition, intracellular inclusions were immunopositive for endogenous Hsp27, and overexpression of this protein reduced aSyn aggregation in a cell culture model.