Matches in SemOpenAlex for { <https://semopenalex.org/work/W1493503901> ?p ?o ?g. }
- W1493503901 endingPage "7551" @default.
- W1493503901 startingPage "7538" @default.
- W1493503901 abstract "Apolipoprotein E4 (ApoE4) is a major genetic risk factor for several neurodegenerative disorders, including Alzheimer's disease (AD). Epigenetic dysregulation, including aberrations in histone acetylation, is also associated with AD. We show here for the first time that ApoE4 increases nuclear translocation of histone deacetylases (HDACs) in human neurons, thereby reducing BDNF expression, whereas ApoE3 increases histone 3 acetylation and upregulates BDNF expression. Amyloid-β (Aβ) oligomers, which have been implicated in AD, caused effects similar to ApoE4. Blocking low-density lipoprotein receptor-related protein 1 (LRP-1) receptor with receptor-associated protein (RAP) or LRP-1 siRNA abolished the ApoE effects. ApoE3 also induced expression of protein kinase C ε (PKCε) and PKCε retained HDACs in the cytosol. PKCε activation and ApoE3 supplementation prevented ApoE4-mediated BDNF downregulation. PKCε activation also reversed Aβ oligomer- and ApoE4-induced nuclear import of HDACs, preventing the loss in BDNF. ApoE4 induced HDAC6-BDNF promoter IV binding, which reduced BDNF exon IV expression. Nuclear HDAC4 and HDAC6 were more abundant in the hippocampus of ApoE4 transgenic mice than in ApoE3 transgenic mice or wild-type controls. Nuclear translocation of HDA6 was also elevated in the hippocampus of AD patients compared with age-matched controls. These results provide new insight into the cause of synaptic loss that is the most important pathologic correlate of cognitive deficits in AD." @default.
- W1493503901 created "2016-06-24" @default.
- W1493503901 creator A5037780581 @default.
- W1493503901 creator A5072355639 @default.
- W1493503901 creator A5075549205 @default.
- W1493503901 date "2015-05-13" @default.
- W1493503901 modified "2023-10-18" @default.
- W1493503901 title "ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation" @default.
- W1493503901 cites W1530376957 @default.
- W1493503901 cites W1577502861 @default.
- W1493503901 cites W1589562788 @default.
- W1493503901 cites W1602494991 @default.
- W1493503901 cites W1722164545 @default.
- W1493503901 cites W1840979539 @default.
- W1493503901 cites W1935334948 @default.
- W1493503901 cites W1965057759 @default.
- W1493503901 cites W1967316112 @default.
- W1493503901 cites W1967397050 @default.
- W1493503901 cites W1972488785 @default.
- W1493503901 cites W1974489486 @default.
- W1493503901 cites W1977212256 @default.
- W1493503901 cites W1977861446 @default.
- W1493503901 cites W1982811047 @default.
- W1493503901 cites W1982889157 @default.
- W1493503901 cites W1989399200 @default.
- W1493503901 cites W1992529363 @default.
- W1493503901 cites W1994535293 @default.
- W1493503901 cites W2002008745 @default.
- W1493503901 cites W2002637584 @default.
- W1493503901 cites W2004470352 @default.
- W1493503901 cites W2004665203 @default.
- W1493503901 cites W2006409771 @default.
- W1493503901 cites W2006534012 @default.
- W1493503901 cites W2011513086 @default.
- W1493503901 cites W2013037750 @default.
- W1493503901 cites W2013178878 @default.
- W1493503901 cites W2017587146 @default.
- W1493503901 cites W2019845642 @default.
- W1493503901 cites W2021181758 @default.
- W1493503901 cites W2023021696 @default.
- W1493503901 cites W2030176492 @default.
- W1493503901 cites W2031379951 @default.
- W1493503901 cites W2038287478 @default.
- W1493503901 cites W2040498799 @default.
- W1493503901 cites W2043355784 @default.
- W1493503901 cites W2047173060 @default.
- W1493503901 cites W2053591294 @default.
- W1493503901 cites W2062574685 @default.
- W1493503901 cites W2069710540 @default.
- W1493503901 cites W2072368655 @default.
- W1493503901 cites W2072583622 @default.
- W1493503901 cites W2073589898 @default.
- W1493503901 cites W2078529082 @default.
- W1493503901 cites W2079965790 @default.
- W1493503901 cites W2081096957 @default.
- W1493503901 cites W2088424318 @default.
- W1493503901 cites W2089448293 @default.
- W1493503901 cites W2090054406 @default.
- W1493503901 cites W2091712128 @default.
- W1493503901 cites W2092577192 @default.
- W1493503901 cites W2099959808 @default.
- W1493503901 cites W2100295360 @default.
- W1493503901 cites W2114570899 @default.
- W1493503901 cites W2117839560 @default.
- W1493503901 cites W2122878223 @default.
- W1493503901 cites W2128565374 @default.
- W1493503901 cites W2129635356 @default.
- W1493503901 cites W2131403086 @default.
- W1493503901 cites W2131975162 @default.
- W1493503901 cites W2132200081 @default.
- W1493503901 cites W2132325550 @default.
- W1493503901 cites W2137116499 @default.
- W1493503901 cites W2140718540 @default.
- W1493503901 cites W2142388403 @default.
- W1493503901 cites W2143955562 @default.
- W1493503901 cites W2145674449 @default.
- W1493503901 cites W2145838320 @default.
- W1493503901 cites W2146070554 @default.
- W1493503901 cites W2151884322 @default.
- W1493503901 cites W2151986987 @default.
- W1493503901 cites W2155045727 @default.
- W1493503901 cites W2165893887 @default.
- W1493503901 cites W2168448928 @default.
- W1493503901 cites W2188111782 @default.
- W1493503901 doi "https://doi.org/10.1523/jneurosci.0260-15.2015" @default.
- W1493503901 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6705431" @default.
- W1493503901 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25972179" @default.
- W1493503901 hasPublicationYear "2015" @default.
- W1493503901 type Work @default.
- W1493503901 sameAs 1493503901 @default.
- W1493503901 citedByCount "102" @default.
- W1493503901 countsByYear W14935039012015 @default.
- W1493503901 countsByYear W14935039012016 @default.
- W1493503901 countsByYear W14935039012017 @default.
- W1493503901 countsByYear W14935039012018 @default.
- W1493503901 countsByYear W14935039012019 @default.
- W1493503901 countsByYear W14935039012020 @default.
- W1493503901 countsByYear W14935039012021 @default.