Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
Int J Mol Sci. 2024 Jul 17;25(14):7815. doi: 10.3390/ijms25147815.
, a digenetic parasite, requires a host and a vector for its life cycle completion. Most species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite's asexual cycle. Studies indicate a species-specific internal clock in , dependent on these host signals. Melatonin, a hormone the pineal gland produces under circadian regulation, impacts various physiological functions and is extensively reviewed as the primary circadian marker affecting parasite rhythms. Research suggests that melatonin facilitates synchronization through the PLC-IP signaling pathway, activating phospholipase C, which triggers intracellular calcium release and gene expression modulation. This evidence strongly supports the role of melatonin as a key circadian marker for parasite synchronization, presenting new possibilities for targeting the melatonin pathway when developing novel therapeutic approaches.
疟原虫是一种双核寄生虫，其生命周期的完成需要宿主和媒介。大多数疟原虫在宿主体内的红细胞内周期中表现出昼夜节律性，有助于免疫逃避。然而，这种节律性在体外培养中减弱，这凸显了宿主衍生信号对于同步寄生虫无性周期的重要性。研究表明， 依赖于这些宿主信号的种特异性内在时钟。褪黑素是松果腺在昼夜节律调节下产生的一种激素，它影响着各种生理功能，并被广泛认为是影响寄生虫节律的主要生物钟标记物。研究表明，褪黑素通过 PLC-IP 信号通路促进同步，激活磷脂酶 C，引发细胞内钙释放和基因表达调节。这一证据有力地支持了褪黑素作为寄生虫同步的关键生物钟标记物的作用，为开发新型治疗方法时靶向褪黑素途径提供了新的可能性。
