Campbell-Galland Adam, Bafna Akanksha, Jagannath Aarti
Sir Jules Thorne Sleep and Circadian Neuroscience Institute, Kavli Institute for Nanoscience Discovery, Nuffield Department of Clinical Neurosciences. University of Oxford. South Parks Road, Oxford OX1 3QU, United Kingdom.
Sir Jules Thorne Sleep and Circadian Neuroscience Institute, Kavli Institute for Nanoscience Discovery, Nuffield Department of Clinical Neurosciences. University of Oxford. South Parks Road, Oxford OX1 3QU, United Kingdom.
Adv Drug Deliv Rev. 2025 Jul 12;224:115653. doi: 10.1016/j.addr.2025.115653.
Circadian rhythms are intrinsic biological processes in all forms of life, governed by a molecular clock, organising physiological and behavioural cycles to align with a 24-hour light-dark cycle. The disruption of these rhythms has been linked to a plethora of neurological conditions and impacting cognitive and metabolic functions. This review offers a clear overview of the genetic and molecular mechanisms that govern the circadian clock. It focuses on the core clock feedback loops, the pathways involved and how these mechanisms are regulated. We explore how clocks in peripheral tissues are synchronised to the suprachiasmatic nucleus and how this is achieved through neuronal and humoral pathways. Additionally, we discuss how dysregulation in circadian rhythms contribute to neurological conditions and potential therapeutic treatments targeting circadian mechanisms. Understanding the mechanisms of circadian dysregulation provides insight into disease pathology and potential therapies. Interventions targeting circadian mechanisms, such as gene and drug delivery systems, show promise to restore rhythms and mitigate neurological symptoms. This review collates current knowledge on circadian biology and its applications addressing neurological dysfunctions, providing a foundation for potential chronotherapeutic interventions.
昼夜节律是所有生命形式中内在的生物过程，由分子时钟控制，组织生理和行为周期以与24小时明暗周期同步。这些节律的破坏与大量神经系统疾病有关，并影响认知和代谢功能。本综述清晰概述了控制昼夜节律时钟的遗传和分子机制。它聚焦于核心时钟反馈回路、涉及的途径以及这些机制是如何被调节的。我们探讨外周组织中的时钟如何与视交叉上核同步，以及这是如何通过神经和体液途径实现的。此外，我们讨论昼夜节律失调如何导致神经系统疾病以及针对昼夜节律机制的潜在治疗方法。了解昼夜节律失调的机制有助于洞察疾病病理学和潜在疗法。针对昼夜节律机制的干预措施，如基因和药物递送系统，有望恢复节律并减轻神经症状。本综述整理了关于昼夜节律生物学及其解决神经功能障碍应用的当前知识，为潜在的时间治疗干预提供了基础。
