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

Yanjue Wu, Zhiming Cao, William L. Klein, Yuan Luo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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 β-amyloid peptide (Aβ) oligomerization has been linked to the pathogenesis of Alzheimer's disease. Previously, we demonstrated that progressive paralysis induced by expression of human Aβ1-42 in transgenic Caenorhabditis elegans was alleviated by Aβ 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 Aβ oligomers in a heat shock time-dependent manner. These results suggest that transient heat shock lessens Aβ toxicity by diminishing Aβ oligomerization, which provides a link between up regulation of endogenous chaperone proteins and protection against Aβ proteotoxicity in vivo.

Original languageEnglish (US)
Pages (from-to)1055-1058
Number of pages4
JournalNeurobiology of Aging
Volume31
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Aβ oligomers Alzheimer's disease
  • C. elegans
  • Heat shock

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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