Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers.

Abstract

Heat shock response, mediated by heat shock proteins, is a highly conserved physiological process in multicellular organisms for reestablishment of cellular homeostasis. Expression of heat shock factors and subsequent heat shock protein plays a role in protection against proteotoxicity in invertebrate and vertebrate models. Proteotoxicity due to beta-amyloid peptide (Abeta) oligomerization has been linked to the pathogenesis of Alzheimer's disease. Previously, we demonstrated that progressive paralysis induced by expression of human Abeta(1-42) in transgenic Caenorhabditis elegans was alleviated by Abeta oligomer inhibitors Ginkgo biloba extract and its constituents [Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M.P., Klein, W.L., Link, C.D., Luo, Y., 2006. Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci. 26(50): 13102-13113]. In this study, we apply a protective heat shock to the transgenic C. elegans and demonstrate: (1) a delay in paralysis, (2) increased expression of small heat shock protein HSP16.2, and (3) significant reduction of Abeta oligomers in a heat shock time-dependent manner. These results suggest that transient heat shock lessens Abeta toxicity by diminishing Abeta oligomerization, which provides a link between up regulation of endogenous chaperone proteins and protection against Abeta proteotoxicity in vivo.

• Authors: Yanjue Wu, Zhiming Cao, William L Klein, Yuan Luo
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 31 Issue 6 Pg. 1055-8 (Jun 2010) ISSN: 1558-1497 [Electronic] United States
• PMID: 18762355 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2008 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antioxidants
• Heat-Shock Proteins
• Peptide Fragments
• Plant Extracts
• amyloid beta-protein (1-42)
• Ginkgo biloba extract
• Hydrogen Peroxide

Topics

• Aging (physiology)
• Amyloid beta-Peptides (genetics, metabolism, toxicity)
• Animals
• Animals, Genetically Modified
• Antioxidants (therapeutic use)
• Behavior, Animal (drug effects)
• Caenorhabditis elegans
• Disease Models, Animal
• Ginkgo biloba
• Heat-Shock Proteins (genetics, metabolism)
• Heat-Shock Response (physiology)
• Hot Temperature
• Humans
• Hydrogen Peroxide (metabolism)
• Molecular Weight
• Paralysis (chemically induced, genetics, prevention & control)
• Peptide Fragments (genetics, metabolism)
• Phytotherapy (methods)
• Plant Extracts (therapeutic use)
• Time Factors