TY - JOUR
T1 - Small heat shock proteins protect against α-synuclein-induced toxicity and aggregation
AU - Outeiro, Tiago Fleming
AU - Klucken, Jochen
AU - Strathearn, Katherine E.
AU - Liu, Fang
AU - Nguyen, Paul
AU - Rochet, Jean Christophe
AU - Hyman, Bradley T.
AU - McLean, Pamela J.
N1 - Funding Information:
T.F.O. is supported by the Tosteson Award Postdoctoral Fellowship from MBRC. This work was sponsored by NIH Grant 5P50-NS38372A-06 (B.T.H.) and NIH Grant ‘R01-NS049221’(J.-C.R.).
PY - 2006/12/22
Y1 - 2006/12/22
N2 - 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.
AB - 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.
KW - Heat shock proteins
KW - Lewy body
KW - Neurodegenerative disease
KW - Parkinson's disease
KW - Protein misfolding
KW - α-Synuclein
UR - http://www.scopus.com/inward/record.url?scp=33751216491&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.10.085
DO - 10.1016/j.bbrc.2006.10.085
M3 - Article
C2 - 17081499
AN - SCOPUS:33751216491
SN - 0006-291X
VL - 351
SP - 631
EP - 638
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -