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10.1016/j.bbadis.2014.05.015 http://scihub22266oqcxt.onion/10.1016/j.bbadis.2014.05.015 C4125440!4125440 !24874077     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24874077 &cmd=llinks): Failed to open stream: HTTP request failed! 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Leptin attenuates BACE1 expression and amyloid-? genesis via the activation of SIRT1 signaling pathway |pdf=|usr=}}{{24874077 }} gab.com Text Leptin attenuates BACE1 expression and amyloid- genesis via the activation of SIRT1 signaling pathway JO: Biochim Biophys Acta http://www.kidney.de/pget.php?&tw=1&pmid=24874077 #FOAvip The aspartyl protease ?-site A?PP-cleaving enzyme 1 (BACE1) catalyzes the rate-limiting step in A? production, a peptide at the nexus of neurodegenerative cascades in Alzheimer Disease (AD). The adipocytokine leptin has been demonstrated to reduce A? production and decrease BACE1 activity and expression levels. However, the signaling cascades involved in the leptin-induced mitigation in A? levels and BACE1 expression levels have not been elucidated. We have demonstrated that the transcription factor nuclear factor - kappa B (NF-?B) positively regulates BACE1 transcription. NF-?B activity is tightly regulated by the mammalian sirtuin SIRT1. Multiple studies have cogently evinced that leptin activates the metabolic master regulator SIRT1. In this study, we determined the extent to which SIRT1 expression and activity regulate the leptin-induced attenuation in BACE1 expression and A? levels in cultured human neuroblastoma SH-SY5Y cells. This study also elucidated and delineated the signal transduction pathways involved in the leptin induced mitigation in BACE1 expression. Our results demonstrate for the first time that leptin attenuates the activation and transcriptional activity of NF-?B by reducing the acetylation of the p65 subunit in a SIRT1-dependent manner. Furthermore, our data shows that leptin reduces the NF-?B-mediated transcription of BACE1 and consequently reduces Amyloid-? genesis. Our study provides a valuable insight and a novel mechanism by which leptin reduces BACE1 expression and Amyloid-? production and may help design potential therapeutic interventions. Twit Text FOAVip Leptin attenuates BACE1 expression and amyloid- genesis via the activation of SIRT1 signaling pathway ????Biochim Biophys Acta http://www.kidney.de/pget.php?&tw=1&pmid=24874077 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24874077 #FOAvip English Wikipedia <ref>{{Cite pmid|24874077 }}</ref> Leptin attenuates BACE1 expression and amyloid-? genesis via the activation of SIRT1 signaling pathway #MMPMID24874077 Marwarha G ; Raza S ; Meiers C ; Ghribi O Biochim Biophys Acta 2014[Sep]; 1842 (9 ): 1587-95 PMID24874077 show ga The aspartyl protease ?-site A?PP-cleaving enzyme 1 (BACE1) catalyzes the rate-limiting step in A? production, a peptide at the nexus of neurodegenerative cascades in Alzheimer Disease (AD). The adipocytokine leptin has been demonstrated to reduce A? production and decrease BACE1 activity and expression levels. However, the signaling cascades involved in the leptin-induced mitigation in A? levels and BACE1 expression levels have not been elucidated. We have demonstrated that the transcription factor nuclear factor - kappa B (NF-?B) positively regulates BACE1 transcription. NF-?B activity is tightly regulated by the mammalian sirtuin SIRT1. Multiple studies have cogently evinced that leptin activates the metabolic master regulator SIRT1. In this study, we determined the extent to which SIRT1 expression and activity regulate the leptin-induced attenuation in BACE1 expression and A? levels in cultured human neuroblastoma SH-SY5Y cells. This study also elucidated and delineated the signal transduction pathways involved in the leptin induced mitigation in BACE1 expression. Our results demonstrate for the first time that leptin attenuates the activation and transcriptional activity of NF-?B by reducing the acetylation of the p65 subunit in a SIRT1-dependent manner. Furthermore, our data shows that leptin reduces the NF-?B-mediated transcription of BACE1 and consequently reduces Amyloid-? genesis. Our study provides a valuable insight and a novel mechanism by which leptin reduces BACE1 expression and Amyloid-? production and may help design potential therapeutic interventions. |Amyloid Precursor Protein Secretases/*genetics/metabolism [MESH] |Amyloid beta-Peptides/*metabolism [MESH] |Aspartic Acid Endopeptidases/*genetics/metabolism [MESH] |Blotting, Western [MESH] |Chromatin Immunoprecipitation [MESH] |Enzyme-Linked Immunosorbent Assay [MESH] |Gene Expression Regulation, Neoplastic/*drug effects [MESH] |Humans [MESH] |Leptin/*pharmacology [MESH] |NF-kappa B/genetics/metabolism [MESH] |Neuroblastoma/*drug therapy/metabolism/pathology [MESH] |Promoter Regions, Genetic [MESH] |RNA, Messenger/genetics [MESH] |Real-Time Polymerase Chain Reaction [MESH] |Reverse Transcriptase Polymerase Chain Reaction [MESH] |Signal Transduction/*drug effects [MESH] |Sirtuin 1/genetics/*metabolism [MESH]Leptin attenuates BACE1 expression and amyloid-? genesis via the activ(epmc).pdf DeepDyve Pubget Overpricing