Modulation of Amyloid-β Protein Precursor Expression by HspB1
| Autor: | Karen M. Mearow, Firoozeh Nafar, Megan Conway, Tatjana Straka |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Time Factors
animal structures Green Fluorescent Proteins BACE1-AS HSP27 Heat-Shock Proteins Enzyme-Linked Immunosorbent Assay Transfection Amyloid beta-Protein Precursor Downregulation and upregulation Heat shock protein Amyloid precursor protein Animals Humans Immunoprecipitation Protein precursor Amyloid beta-Peptides biology Chemistry General Neuroscience P3 peptide General Medicine Peptide Fragments Biochemistry of Alzheimer's disease Cell biology Psychiatry and Mental health Clinical Psychology HEK293 Cells Gene Expression Regulation Mutation biology.protein Geriatrics and Gerontology Amyloid precursor protein secretase |
| Zdroj: | Journal of Alzheimer's Disease. 42:435-450 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-140348 |
| Popis: | Upregulation of heat shock proteins, such as Hsp70 and HspB1/Hsp27, have been associated with an amelioration of the deficits in animal models of Alzheimer's disease (AD). HspB1 is reported to be increased in AD brains and to accumulate in plaques, but whether this localization is an attempt by HspB1 to ameliorate the detrimental effects of amyloid-β (Aβ) on cells or part of the disease process is unknown. Here we explore the potential effects of the HspB1 on amyloid-β protein precursor (AβPP) processing and distribution within HEK293 stable cell lines expressing either AβPPwt or AβPPsw. We compare AβPP production, distribution, and release of proteolytic products (including Aβ40 and Aβ42) to determine possible modifications in the presence of HspB1. We also investigate whether HspB1 interacts with Aβ or its precursor, AβPP, and whether, through this interaction, it is able to alter AβPP processing or release of Aβ peptide. Coexpression of HspB1 resulted in increased cellular holoAβPP as well as C-terminal fragments. Further, expression of HspB1 attenuated the release of Aβ42 from the AβPPsw cells. In summary, we have shown that expression of HspB1 alters AβPP expression and processing in cell lines expressing AβPPwt and AβPPsw. Furthermore, the presence of HspB1 decreased the amount of Aβ42 released by the cell lines. Thus in addition to its effects on protecting cells from the potentially toxic effects of Aβ, HspB1 also appears to be involved in modulating cellular levels of AβPP, although an understanding of the underlying mechanisms requires further investigation. |
| Databáze: | OpenAIRE |
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