最先端研究セミナー

講演者：土居 雅夫（京都大学大学院薬学研究科 　教授）

演題：Reactivating Circadian Rhythms as a Therapeutic Strategy: Insights from Basic Research

日時：2025年9月10日（水）　12：00-13：00

開催場所：発生医学研究所1階　カンファレンス室

※薬学部中継なし

※ZOOMミーティングのURLはMoodleの「S-HIGO最先端研究セミナーA、B」にてご確認ください。

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract:One of the most significant conceptual changes brought about by the discovery of clock genes and development of circadian-clock mutant mice is the recognition that impaired circadian rhythmicity extends its impact beyond sleep, driving pathogenesis of a wide variety of disorders such as cancer, obesity, and hypertension. However, despite this growing clinical evidence, chronobiology still lacks a coherent answer to the converse question: can restoration of circadian rhythms ameliorate—or even reverse—such diseases? Here, in my talk, three complementary pharmacological strategies—each still in preclinical development—will be explored. First, direct modulation of the transcription-translation feedback loop (TTFL)—the core gene-regulatory circuit that generates 24-hour rhythms in almost all nucleated cells—is reviewed as an approach to manipulation of cellular circadian biology. Second, the suprachiasmatic nucleus (SCN)-enriched G-protein-coupled receptor Gpr176 is highlighted as a central-clock target, given its ligand-independent, Gz-mediated control of cAMP signaling and demonstrated ability to reset the master pacemaker. Third, the concept of rhythmic enhancement of output function is introduced and exemplified by describing re-activation of circadian NAD⁺-dependent 3β-HSD activity in the meibomian gland—using nicotinamide mononucleotide (NMN)—to restore peripheral clock-driven steroidogenesis in this tissue, which leads to amelioration of meibomian gland dysfunction, a leading cause of dry eye disease. In my talk, I will highlight the molecular logic of each strategy; both mechanistic insights and safety-efficacy considerations will be discussed.

担当分野：薬学生化学　土屋（4359)