{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:03:42Z","timestamp":1785225822198,"version":"3.55.0"},"reference-count":91,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Oriental Talent Plan 2025","award":["BJWS2025077"],"award-info":[{"award-number":["BJWS2025077"]}]},{"name":"Shanghai Medical Innovation and Development Foundation","award":["SMIDF-106-2024A5"],"award-info":[{"award-number":["SMIDF-106-2024A5"]}]},{"DOI":"10.13039\/501100008750","name":"Shanghai Shenkang Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC2023CRD005"],"award-info":[{"award-number":["SHDC2023CRD005"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Institute of Mental Diseases","award":["SZB2022101"],"award-info":[{"award-number":["SZB2022101"]}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2024QN046"],"award-info":[{"award-number":["2024QN046"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder in which circadian rhythm disruption (CRD) emerges as both a prodromal feature and a potential pathogenic driver. Elucidating the bidirectional interplay between PD and CRD is essential for identifying early biomarkers and developing chronotherapeutic strategies. We narratively synthesized literature published over the past two decades in PubMed, Web of Science, and CNKI, focusing on molecular mechanisms, clinical manifestations, biomarker development, and interventional studies addressing the PD\u2013CRD interface. In the CRD-PD direction, circadian disruption accelerates dopaminergic neurodegeneration through four convergent mechanisms: (i) REV-ERB\u03b1\u2013mediated dysregulation of dopamine biosynthesis and NF-\u03baB\/NLRP3-driven neuroinflammation; (ii) impaired sleep-dependent glymphatic clearance of \u03b1-synuclein (\u03b1-syn); (iii) NAD+\u2013SIRT1\u2013BMAL1\u2013PGC-1\u03b1 axis dysfunction leading to mitochondrial bioenergetic failure; and (iv) C\/EBP\u03b2-dependent autophagic rhythm disruption coupled with pro-inflammatory microglial activation, collectively establishing a dual pro-inflammatory\u2013autophagy-suppressive milieu permissive for \u03b1-syn aggregation. In the reverse PD-CRD direction, PD pathology destabilizes the circadian system via Braak-stage degeneration of rhythm-regulatory nuclei, retinal dopaminergic denervation attenuating SCN photic entrainment, pineal\u2013melatonin axis suppression, iatrogenic effects of dopaminergic pharmacotherapy, and gut microbiota dysbiosis propagated through the microbiota\u2013gut\u2013brain axis. Emerging multi-modal chronobiomarkers\u2014including peripheral clock gene expression profiles, melatonin secretion patterns, tryptophan\u2013kynurenine metabolites, and gut microbial oscillation signatures\u2014show promise for prodromal diagnosis and disease subtyping. Circadian-targeted precision interventions\u2014encompassing timed bright light therapy, exogenous melatonin, and chronopharmacological interventions\u2014represent a promising translational paradigm for the early identification and management of PD.<\/jats:p>","DOI":"10.3390\/ijms27156719","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"6719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bidirectional Mechanisms Linking Circadian Rhythm Disruption and Parkinson\u2019s Disease: Chronobiomarkers and Therapeutic Implications"],"prefix":"10.3390","volume":"27","author":[{"given":"Xinyue","family":"Zhang","sequence":"first","affiliation":[{"name":"Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Shen","sequence":"additional","affiliation":[{"name":"Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wu","sequence":"additional","affiliation":[{"name":"Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ye","sequence":"additional","affiliation":[{"name":"Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1056\/NEJMra2401857","article-title":"Parkinson\u2019s Disease","volume":"391","author":"Tanner","year":"2024","journal-title":"N. 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