{"id":3566,"date":"2019-04-24T11:15:00","date_gmt":"2019-04-24T18:15:00","guid":{"rendered":"https:\/\/dornsife.usc.edu\/news\/stories\/a-good-nights-sleep-may-be-in-sight\/"},"modified":"2025-02-14T16:31:49","modified_gmt":"2025-02-15T00:31:49","slug":"researchers-to-develop-new-sleep-disorder-treatments","status":"publish","type":"post","link":"https:\/\/dornsife.usc.edu\/news\/stories\/researchers-to-develop-new-sleep-disorder-treatments\/","title":{"rendered":"A good night\u2019s sleep may be in sight"},"content":{"rendered":"\n\n\n    \n                                \n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-hero \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-hero\"\n    \n      >\n\n    \n<div class=\"inner-wrapper\">\n          \n<div class=\"f--field f--image\">\n\n    \n    \n    \n    \n    \n    \n              \n      <img\n                            data-src=\"https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2023\/04\/story-2999-768x432.jpg\"\n          data-srcset=\"https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2023\/04\/story-2999-768x432.jpg 768w\"          data-sizes=\"(min-width:1200px) 75vw, (min-width:768px) 83vw, 100vw\"          class=\"lazyload\"\n        \n                  alt=\"A good night\u2019s sleep may be in sight\"\n        \n        \n                                      \/>\n\n    \n    \n  \n  \n\n<\/div>\n  \n      <div class=\"image-caption\">\n          \n<div class=\"f--field f--description\">\n\n    \n  The sleep-promoting hormone melatonin (shown as a constellation in the night sky) is synthesized at night from serotonin (shown as a kite). High melatonin levels at night permit the molecule to establish its sleep-promoting properties by acting through high-affinity receptors, depicted at right. (Illustration: Yekaterina Kadyshevskaya.)\n\n\n<\/div>\n    <\/div>\n  \n  <div class=\"text-wrapper\">\n          <nav aria-label=\"Breadcrumb\" class=\"breadcrumbs\">\n        <ul>\n                      <li><a href=\"\/news\/stories\/\">News<\/a><\/li>\n                      <li><a href=\"\/news\/stories\/\/?category=faculty\">Faculty<\/a><\/li>\n                  <\/ul>\n      <\/nav>\n    \n              \n<div class=\"f--field f--page-title\">\n\n    \n  <h1>A good night\u2019s sleep may be in sight<\/h1>\n\n\n<\/div>\n    \n          <div class=\"subtitle\">\n            \n<div class=\"f--field f--description\">\n\n    \n  Researchers plan to develop new sleep disorder treatments based on new 3D models of two melatonin receptors created by an international team. The studies were published in \u2018Nature\u2019 this week. <strong>[3\u00bc min read]<\/strong>\n\n\n<\/div>\n      <\/div>\n    \n           <strong class=\"author-field\"><span >By<\/span><a href=\"mailto:communication@dornsife.usc.edu\">Emily Gersema<\/a><\/strong>\n    \n          <span class=\"post-date-field\">April 24, 2019<\/span>\n      <\/div>\n<\/div>\n\n\n  <\/div><\/div>\n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--social-share \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--social-share\"\n    \n      >\n\n    \n  <div class=\"content-wrapper\">\n    <span class=\"a2a_kit a2a_kit_size_32 addtoany_list\" style=\"line-height: 32px;\">\n      <span class=\"title\">\n        Share\n      <\/span>\n                        <a class=\"a2a_button_copy_link\" target=\"_blank\" href=\"\/#copy_link\" rel=\"nofollow noopener\" title=\"Link\">\n            <span class=\"a2a_svg a2a_s__default a2a_s_copy_link\">\n              <svg 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cc--rich-text \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--rich-text\"\n    \n      >\n\n    \n      \n<div class=\"f--field f--wysiwyg\">\n\n    \n  <p>A third of all Americans have difficulty with sleeping, and many of them turn to melatonin supplements to catch some Zs. However, scientists don\u2019t fully understand melatonin\u2019s role in the biological clock, which has made it difficult to develop drugs for sleep disorders without several side effects.<\/p>\n<p>Now an international team of scientists has shed much-needed light on melatonin\u2019s effects, opening the door to the development of new drugs for sleep disorders \u2014\u00a0and other health issues affected by melatonin. They determined 3D models of the tiny antennae \u2014 called receptors \u2014 on the surface of cells that synchronize the body\u2019s internal clock with the day and night cycle.<\/p>\n<p>\u201cOur goal is to provide the structural information to other researchers who can use it for designing new drug compounds or study mutations of these receptors in patients,\u201d said corresponding author Vadim Cherezov, a scientist at the <a href=\"https:\/\/dornsife.usc.edu\/bridge-institute\/\" target=\"_blank\" rel=\"noopener\">Bridge Institute<\/a> at USC Michelson Center for Convergent Bioscience.<\/p>\n<p>Creating the 3D maps of the two melatonin receptors, MT1 and MT2, is critical for understanding how the biological clock works. The scientists can use this information to design drug molecules that bind to the melatonin receptors and monitor the potential effects. The benefits could go beyond improving sleep.<\/p>\n<p>\u201cThere have been several mutations identified in the MT2 receptor that are associated with type 2 diabetes,\u201d said Linda Johansson, a research associate at the Bridge Institute and at USC Dornsife\u2019s Department of Chemistry. \u201cThat also would be important to understand.\u201d<\/p>\n<p>These 3D models also enable the scientists to improve the efficiency of potential new drug treatments and reduce their side effects, even before they begin testing them in animal studies.<\/p>\n<p>The findings on the melatonin receptors were published on April 24 in the journal <em><a href=\"http:\/\/dx.doi.org\/10.1038\/s41586-019-1141-3\" target=\"_blank\" rel=\"noopener\">Nature<\/a><\/em>.<\/p>\n<h2>Melatonin comes from the \u2018soul\u2019<\/h2>\n<p>Melatonin is generated in the center of the brain by the pineal gland, once described by the philosopher Descartes as the \u201csoul\u201d of the brain and body.<\/p>\n<figure style=\"width: 250px\" class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"\/wp-content\/uploads\/sites\/7\/migration-uploads\/Melatonin_Secondary-2999.jpg\" alt=\"Drawing of a cat sleeping curled around a drawing of a melatonin molecule.\" width=\"250\" height=\"433\" \/><figcaption class=\"wp-caption-text\">A sleeping cat cradles melatonin, the sleep molecule. (Illustration: Crystal Jow.)<\/figcaption><\/figure>\n<p>Humans respond naturally to daylight changes through the pineal gland, near the hypothalamus. As night falls, the gland produces more melatonin, which then binds to the MT1 and MT2 receptors of the cells. Before dawn, the gland decreases melatonin levels, signaling that it\u2019s time to wake.<\/p>\n<h2>Two of hundreds<\/h2>\n<p>MT1 and MT2 are among an estimated 800 receptors in the human body. These receptors, known as \u201cG protein-coupled receptors,\u201d (GPCRs) appear on the surface of a cell. They act as a sort of email inbox, relaying information into the cell to set off a cascade of activity.<\/p>\n<p>About a third of all drugs on the market are designed to bind with GPCRs. Each receptor has a different role in regulating functions in the body, many of which are critical for basic survival, such as hunger and reproductivity. The bulk of these receptors also have some role in the human olfactory system \u2014 taste and smell.<\/p>\n<p>Scientists around the world have obtained structures of less than one tenth of these receptors so far. MT1 and MT2 are among the latest.<\/p>\n<p>Having models of their structures could have implications beyond circadian rhythms. \u201cThe MT1 and MT2 receptors certainly regulate other processes,\u201d said Benjamin Stauch, a research associate at the Bridge Institute and at USC Dornsife\u2019s Department of Chemistry.<\/p>\n<p>\u201cFor example, they modulate the immune system, reproductive functions and they are associated with some cancers.\u201d<\/p>\n<p>&#8220;By comparing the 3D structures of the MT1 and MT2 receptors, we can better discern the unique, structural differences that distinguish the two receptors from each other \u2014 and their roles in the biological clock,\u201d said Wei Liu of Arizona State University\u2019s Biodesign Institute. \u201cArmed with this knowledge, it becomes easier to design drug-like molecules that will bind to only one receptor or the other, but not both. This selective binding is important as it will minimize unwanted side-effects.\u201d<\/p>\n<h2>About the study<\/h2>\n<p>The study is the result of a collaboration among scientists at USC, Arizona State University\u2019s Biodesign Institute and Department of Physics, SLAC National Accelerator Laboratory, University of Buffalo, University of North Carolina, and the Universit\u00e9 de Lille in France.<\/p>\n<p>The work was supported by National Institutes of Health grants (R35 GM127086, R21 DA042298, R01 GM124152, and U24DK116195), the NIMH Psychoactive Drug Screening Program (contract F31-NS093917), the National Science Foundation BioXFEL Science and Technology Center 1231306, EMBO ALTF 677-2014, HFSP long-term fellowship LT000046\/2014-L, and a postdoctoral fellowship from the Swedish Research Council, SLAC, supported by the U.S. Department of Energy\u2019s Office of Science via contract DE-AC02-76SF00515.<\/p>\n\n\n\n<\/div>\n\n\n  <\/div><\/div>\n\n\n\n  \n        \n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-related-stories \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-related-stories\"\n    \n      >\n\n    \n  <div class=\"inner-wrapper\">\n    \n                  <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/scott-fraser-appointed-chan-zuckerberg-initiative\/\" \n                        class=\"\" \n      >USC professor Scott Fraser appointed to leadership role at Chan Zuckerberg Initiative<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n              <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/structural-biologist-helen-berman-elected-national-academy-of-sciences\/\" \n                        class=\"\" \n      >Structural biologist Helen Berman elected to the National Academy of Sciences<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n              <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/global-collaboration-cure-diabetes\/\" \n                        class=\"\" \n      >New professor rides waves of discovery to decode cellular activity underlying diabetes<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n            <\/div>\n\n\n  <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Researchers plan to develop new sleep disorder treatments based on new 3D models of two melatonin receptors created by an international team. The studies were published in \u2018Nature\u2019 this week. <strong>[3\u00bc min read]<\/strong><\/p>\n","protected":false},"author":52,"featured_media":3569,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[10],"tags":[399,480,202,370,738],"class_list":["post-3566","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-faculty","tag-bridge-institute","tag-health","tag-michelson-center-for-convergent-bioscience","tag-science","tag-vadim-cherezov"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>A good night\u2019s sleep may be in sight<\/title>\n<meta name=\"description\" content=\"Researchers plan to develop new sleep disorder treatments based on new 3D models of two melatonin receptors created by an international team. 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