{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:38:26Z","timestamp":1789349906732,"version":"build-2803163510"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,2,28]]},"abstract":"<jats:p>\n                    N-acetylserotonin (NAS) is synthesized from serotonin by arylalkylamine\n                    <jats:italic>N<\/jats:italic>\n                    -acetyltransferase (AANAT), which is predominantly expressed in the pineal gland and retina. NAS activates TrkB in a circadian manner and exhibits antidepressant effects in a TrkB-dependent manner. It also enhances neurogenesis in hippocampus in sleep-deprived mice. Here we report the identification of NAS derivatives that possess much more robust neurotrophic effects with improved pharmacokinetic profiles. The compound\n                    <jats:italic>N<\/jats:italic>\n                    -[2-(5-\n                    <jats:underline>h<\/jats:underline>\n                    ydroxy-1H-\n                    <jats:underline>i<\/jats:underline>\n                    ndol-3-yl)ethyl]-2-\n                    <jats:underline>o<\/jats:underline>\n                    xopiperidine-3-\n                    <jats:underline>c<\/jats:underline>\n                    arboxamide (HIOC) selectively activates TrkB receptor with greater potency than NAS. It potently protects retinas from light-induced retinal degeneration (LIRD), which is tightly coupled with pronounced TrkB activation in retinas. Pharmacokinetic studies demonstrate that this compound is stable in serum and liver microsomes. It can pass the blood\u2013brain barrier and blood\u2013retinal barrier. Hence, HIOC is a good lead compound for further drug development for treating retinal degenerative diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1119201109","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T00:11:40Z","timestamp":1329178300000},"page":"3540-3545","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["<i>N<\/i>\n                    -acetyl serotonin derivatives as potent neuroprotectants for retinas"],"prefix":"10.1073","volume":"109","author":[{"given":"Jianying","family":"Shen","sequence":"first","affiliation":[{"name":"Departments of aPathology and Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanika","family":"Ghai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradoldej","family":"Sompol","sequence":"additional","affiliation":[{"name":"Departments of aPathology and Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of aPathology and Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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