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10.1038/s41598-017-04144-3 http://scihub22266oqcxt.onion/10.1038/s41598-017-04144-3 C5504036!5504036!28694424     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28694424&cmd=llinks): Failed to open stream: HTTP request failed! 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A tricyclic antidepressant, amoxapine, reduces amyloid-? generation through multiple serotonin receptor 6-mediated targets |pdf=|usr=}}{{28694424}} gab.com Text A tricyclic antidepressant, amoxapine, reduces amyloid- generation through multiple serotonin receptor 6-mediated targets JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=28694424 #FOAvip Alzheimer?s disease (AD) is a major and devastating neurodegenerative disease, and the amyloid-? (A?) hypothesis is still the central theory for AD pathogenesis. Meanwhile, another major mental illness, depression, is one of the risk factors for AD. From a high-throughput screening (HTS), amoxapine, a typical secondary amine tricyclic antidepressant (TCA), was identified to reduce A? production. A follow-up investigation on antidepressants showed that most of the TCAs harbour similar activity. Previous studies have indicated that TCAs improve cognitive function in AD mouse models as well as in preliminary clinical data; however, the underlying mechanism is controversial, and the effect on A? is elusive. Thus, we developed a secondary screening to determine the molecular target of amoxapine, and serotonin receptor 6 (HTR6) was identified. Knockdown of HTR6 reduced the amoxapine?s effect, while the HTR6 antagonist SB258585 mimicked the activity of amoxapine. Further mechanistic study showed that amoxapine and SB258585 reduced A? generation through multiple HTR6-mediated targets, including ?-arrestin2 and CDK5. Taken together, our study suggests that amoxapine, though no longer a first-line drug for the treatment of depression, may be beneficial for AD and further structural modification of TCAs may lead to desirable therapeutic agents to treat both AD and depression. Twit Text FOAVip A tricyclic antidepressant, amoxapine, reduces amyloid- generation through multiple serotonin receptor 6-mediated targets ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=28694424 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28694424 #FOAvip English Wikipedia <ref>{{Cite pmid|28694424}}</ref> A tricyclic antidepressant, amoxapine, reduces amyloid-? generation through multiple serotonin receptor 6-mediated targets #MMPMID28694424 Li X; Wang Q; Hu T; Wang Y; Zhao J; Lu J; Pei G Sci Rep 2017[]; 7 (ä): ä PMID28694424show ga Alzheimer?s disease (AD) is a major and devastating neurodegenerative disease, and the amyloid-? (A?) hypothesis is still the central theory for AD pathogenesis. Meanwhile, another major mental illness, depression, is one of the risk factors for AD. From a high-throughput screening (HTS), amoxapine, a typical secondary amine tricyclic antidepressant (TCA), was identified to reduce A? production. A follow-up investigation on antidepressants showed that most of the TCAs harbour similar activity. Previous studies have indicated that TCAs improve cognitive function in AD mouse models as well as in preliminary clinical data; however, the underlying mechanism is controversial, and the effect on A? is elusive. Thus, we developed a secondary screening to determine the molecular target of amoxapine, and serotonin receptor 6 (HTR6) was identified. Knockdown of HTR6 reduced the amoxapine?s effect, while the HTR6 antagonist SB258585 mimicked the activity of amoxapine. Further mechanistic study showed that amoxapine and SB258585 reduced A? generation through multiple HTR6-mediated targets, including ?-arrestin2 and CDK5. Taken together, our study suggests that amoxapine, though no longer a first-line drug for the treatment of depression, may be beneficial for AD and further structural modification of TCAs may lead to desirable therapeutic agents to treat both AD and depression. äA tricyclic antidepressant, amoxapine, reduces amyloid-? generation th(epmc).pdf DeepDyve Pubget Overpricing