{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:23:26Z","timestamp":1790706206101,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771521"],"award-info":[{"award-number":["81771521"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21876169"],"award-info":[{"award-number":["21876169"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson\u2019s disease (PD) patients.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We determined the expression profiles of five principal clock genes, <jats:italic>BMAL1<\/jats:italic>, <jats:italic>CLOCK<\/jats:italic>, <jats:italic>CRY1<\/jats:italic>, <jats:italic>PER1<\/jats:italic>, and <jats:italic>PER2<\/jats:italic>, in the peripheral blood mononuclear cells (PBMCs) of PD patients (<jats:italic>n<\/jats:italic> = 326), and healthy controls (HC, <jats:italic>n<\/jats:italic> = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Our data showed that the expression levels of <jats:italic>BMAL1<\/jats:italic>, <jats:italic>CLOCK<\/jats:italic>, <jats:italic>CRY1<\/jats:italic>, <jats:italic>PER1<\/jats:italic>, and <jats:italic>PER2<\/jats:italic> were significantly decreased in the PBMCs of PD as compared with that of HC (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). PD patients had reduced plasma melatonin levels compared with HC (<jats:italic>P<\/jats:italic> &amp;lt; 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes (<jats:italic>r<\/jats:italic> = \u22120.344\u223c\u22120.789, <jats:italic>P<\/jats:italic> &amp;lt; 0.01) and melatonin concentration (<jats:italic>r<\/jats:italic> = \u22120.509\u223c\u22120.753, <jats:italic>P<\/jats:italic> &amp;lt; 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This case-control study demonstrates that peripheral <jats:italic>BMAL1<\/jats:italic>, <jats:italic>CLOCK<\/jats:italic>, <jats:italic>CRY1<\/jats:italic>, <jats:italic>PER1, PER2<\/jats:italic>, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.<\/jats:p>","DOI":"10.3389\/fnagi.2021.736026","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T18:28:19Z","timestamp":1633112899000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":42,"title":["Peripheral Clock System Abnormalities in Patients With Parkinson\u2019s Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Tianbai","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murad","family":"Al-Nusaif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.biopsych.2009.12.026","article-title":"CLOCK gene variants associate with sleep duration in two independent populations.","volume":"67","author":"Allebrandt","year":"2010","journal-title":"Biol. 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