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• W2056373089 startingPage "e37755" @default.
• W2056373089 abstract "Heat shock proteins (Hsps) are a set of molecular chaperones involved in cellular repair. They provide protective mechanisms that allow cells to survive potentially lethal insults, In response to a conditioning stress their expression is increased. Here we examined the connection between Hsps and Aβ42, the amyloid peptide involved in the pathological sequence of Alzheimer’s disease (AD). Extracellular Aβ42 associates with neuronal cells and is a major constituent of senile plaques, one of the hallmarks of AD. Although Hsps are generally thought to prevent accumulation of misfolded proteins, there is a lack of mechanistic evidence that heat shock chaperones directly modulate Aβ42 toxicity. In this study we show that neither extracellular Aβ42 nor Aβ42/PrPC trigger the heat shock response in neurons. To address the influence of the neuroprotective heat shock response on cellular Aβ42, Western analysis of Aβ42 was performed following external Aβ42 application. Five hours after a conditioning heat shock, Aβ42 association with CAD cells was increased compared to control neurons. However, at forty-eight hours following heat shock Aβ42 levels were reduced compared to that found for control cells. Moreover, transient transfection of the stress induced Hsp40, decreased CAD levels of Aβ42. In contrast to CAD cells, hippocampal neurons transfected with Hsp40 retained Aβ42 indicating that Hsp40 modulation of Aβ42 proteostasis is cell specific. Mutation of the conserved HPD motif within Hsp40 significantly reduced the Hsp40-mediated Aβ42 increase in hippocampal cultures indicating the importance of this motif in regulating cellular Aβ42. Our data reveal a biochemical link between Hsp40 expression and Aβ42 proteostasis that is cell specific. Therefore, increasing Hsp40 therapeutically with the intention of interfering with the pathogenic cascade leading to neurodegeneration in AD should be pursued with caution." @default.
• W2056373089 created "2016-06-24" @default.
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• W2056373089 date "2012-05-29" @default.
• W2056373089 modified "2023-10-02" @default.
• W2056373089 title "Cell Line Specific Modulation of Extracellular Aβ42 by Hsp40" @default.
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• W2056373089 doi "https://doi.org/10.1371/journal.pone.0037755" @default.
• W2056373089 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3362613" @default.
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• W2056373089 hasPublicationYear "2012" @default.
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