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Review
. 2014:2014:796869.
doi: 10.1155/2014/796869. Epub 2014 Oct 13.

Heat shock protein 90 in Alzheimer's disease

Jiang-Rong Ou  1 , Meng-Shan Tan  2 , An-Mu Xie  3 , Jin-Tai Yu  4 , Lan Tan  4
Affiliations
Review

Heat shock protein 90 in Alzheimer's disease

Jiang-Rong Ou et al. Biomed Res Int. 2014.

Abstract

Alzheimer's disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aβ) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response. In AD, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70. Therefore, we review here to further discuss the recent advances and challenges in targeting Hsp90 for AD therapy.

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Figures

Figure 1
Figure 1
Possible roles of Hsp90 in AD. The two hallmarks of the pathology of AD are the extracellular aggregated Aβ and the intracellular microtubule-associated protein tau. Hsp90 plays a key role in preventing protein misfolding and aggregation. Hsp90 can increase the clearance of Aβ peptides and facilitate Aβ degradation by the activation of TLR4 pathway, the formation of the complex of Hsp90 and HSP70/HSP40, and inducing the production of IL-6 and TNFα. In addition, Akt and CHIP coregulate tau degradation through coordinated interactions. Aberrant activation of kinases such as CDK5 and GSK3β can cause phosphorylation of tau. The possible roles of Hsp90 in AD pathogenesis may open a novel therapeutic target for AD.
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References

    1. Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annual Review of Pharmacology and Toxicology. 2003;43:545–584. - PubMed
    1. Paul S, Mahanta S. Association of heat-shock proteins in various neurodegenerative disorders: is it a master key to open the therapeutic door? Molecular and Cellular Biochemistry. 2014;386(1-2):45–61. - PubMed
    1. Johnson JL. Evolution and function of diverse Hsp90 homologs and cochaperone proteins. Biochimica et Biophysica Acta. 2012;1823(3):607–613. - PubMed
    1. Kakimura J-I, Kitamura Y, Takata K, et al. Microglial activation and amyloid-β clearance induced by exogenous heat-shock proteins. The FASEB Journal. 2002;16(6):601–603. - PubMed
    1. Dickey CA, Kamal A, Lundgren K, et al. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. The Journal of Clinical Investigation. 2007;117(3):648–658. - PMC - PubMed

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