Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers.
Neurobiol Aging
; 31(6): 1055-8, 2010 Jun.
Article
in En
| MEDLINE
| ID: mdl-18762355
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.
Full text:
1
Database:
MEDLINE
Therapeutic Methods and Therapies TCIM:
Terapias_biologicas
Main subject:
Paralysis
/
Behavior, Animal
/
Amyloid beta-Peptides
/
Heat-Shock Response
Type of study:
Prognostic_studies
Language:
En
Journal:
Neurobiol Aging
Year:
2010
Type:
Article
Affiliation country:
United States