{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:23:25Z","timestamp":1790619805524,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010023","name":"Natural Science Research of Jiangsu Higher Education Institutions of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010023","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016802","name":"Natural Science Foundation of Changzhou City Graduate Research and Innovation Projects of Jiangsu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cutaneous pigmentation was recently shown to be an event regulated by clock proteins. Cryptochrome (CRY) is a key protein composing the feedback loop of circadian clock, however, the function of CRY in melanocytes remains unclear. Here, we found that KL001, a synthetic small molecule modulator of CRY1, inhibited melanin synthesis, as well as reduced melanocyte dendrite elongation and melanosome transport. In addition, the dominant role of CRY1 in KL001-induced anti-melanogenesis was revealed by small interfering RNA transfection. Cellular tyrosinase activity and expression level of melanogenic proteins, including tyrosinase, TRP-1, TRP-2, and transport proteins like Rab27a, Cdc42 and Myosin Va induced by \u03b1-MSH were remarkably reversed after KL001 treatment. Mechanistically, CRY1 activation inhibited melanogenesis through CREB-dependent downregulation of MITF and CREB phosphorylation was mediated by classical cAMP\/PKA pathway. In addition, the other CRY1 activator, KL044 also suppressed cAMP\/PKA\/CREB pathway and inhibited melanogenesis. Finally, anti-melanogenic efficacy of KL001 was confirmed by determination of melanin contents in UVB-tanning model of brown guinea pigs, which indicated that targeting CRY1 activity, <jats:italic>via<\/jats:italic> topical application of small molecule activator, can be utilized therapeutically to manage human pigmentary disorders.<\/jats:p>","DOI":"10.3389\/fphar.2023.1081030","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T06:13:52Z","timestamp":1675664032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Cryptochrome 1 activation inhibits melanogenesis and melanosome transport through negative regulation of cAMP\/PKA\/CREB signaling pathway"],"prefix":"10.3389","volume":"14","author":[{"given":"Rongyin","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/exd.14231","article-title":"Cryptochrome 1 is modulated by blue light in human keratinocytes and exerts positive impact on human hair growth","volume":"30","author":"Buscone","year":"2021","journal-title":"Exp. 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