Bibliographic Citation
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DOI | 10.1016/j.bbrc.2006.10.085 |
Title | Small heat shock proteins protect against {alpha}-synuclein-induced toxicity and aggregation |
Creator/Author | Outeiro, Tiago Fleming [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States)] ; Klucken, Jochen [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States)] ; Strathearn, Katherine E. [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2091 (United States)] ; Liu Fang [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2091 (United States)] ; Nguyen, Paul [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States)] ; Rochet, Jean-Christophe [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2091 (United States)] ; Hyman, Bradley T. [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States)] ; McLean, Pamela J. [Alzheimer's Research Unit, MassGeneral Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129 (United States)]. E-mail: touteiro@partners.org |
Publication Date | 2006 Dec 22 |
OSTI Identifier | OSTI ID: 20857925 |
Other Number(s) | Journal ID: ISSN 0006-291X; BBRCA9; TRN: US07R0409030105 |
Resource Type | Journal Article |
Resource Relation | Journal: Biochemical and Biophysical Research Communications; Journal Volume: 351; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.10.085; PII: S0006-291X(06)02327-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA) |
Subject | 60 APPLIED LIFE SCIENCES; AGGLOMERATION; CELL CULTURES; HEAT-SHOCK PROTEINS; MESSENGER-RNA; NERVOUS SYSTEM DISEASES; POLYMERASE CHAIN REACTION; QUALITY CONTROL; TOXICITY |
Description/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). {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. |
Country of Publication | United States |
Language | English |
Format | Size: page(s) 631-638 |
System Entry Date | 2007 May 07 |
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