Khayatan Danial, Razavi Seyed Mehrad, Arab Zahra Najafi, Nasoori Hadis, Fouladi Abtin, Pasha Aytak Vahdat Khajeh, Butler Alexandra E, Karav Sercan, Momtaz Saeideh, Abdolghaffari Amir Hossein, Sahebkar Amirhossein
Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Inflammopharmacology. 2025 Apr;33(4):1583-1616. doi: 10.1007/s10787-025-01643-y. Epub 2025 Feb 16.
The mammalian target of rapamycin (mTOR) is a crucial enzyme in regulating multiple signaling pathways in the body, including autophagy, proliferation and apoptosis. Disruption of these mTOR signaling pathways can lead to an array of abnormalities and trigger disease processes, examples being neurodegenerative conditions, cancer, obesity and diabetes. Under conditions of oxidative stress, mTOR can regulate apoptosis and autophagy, with tissue repair being favored under such circumstances. Moreover, the correlation between mTOR and other signaling pathways could play a pivotal role in the pathophysiology of numerous disorders. mTOR has a tight connection with NF-κB, Akt, PI3K, MAPK, GSK-3β, Nrf2/HO-1, JAK/STAT, CREB/BDNF, and ERK1/2 pathways, which together could play significant roles in the regulation of inflammation, apoptosis, cell survival, and oxidative stress in different body organs. Research suggests that inhibiting mTOR could be beneficial in treating metabolic, neurological and cardiovascular conditions, as well as potentially extending life expectancy. Therefore, identifying new chemicals and agents that can modulate the mTOR signaling pathway holds promise for treating and preventing these disorders. Curcumin is one such agent that has demonstrated regulatory effects on the mTOR pathway, making it an exciting alternative for reducing complications associated with complex diseases by targeting mTOR. This review aims to examine the potential of curcumin in modulating the mTOR signaling pathway and its therapeutic implications.
雷帕霉素的哺乳动物靶点(mTOR)是调节体内多种信号通路的关键酶,这些信号通路包括自噬、增殖和凋亡。这些mTOR信号通路的破坏会导致一系列异常并引发疾病进程,如神经退行性疾病、癌症、肥胖症和糖尿病。在氧化应激条件下,mTOR可以调节凋亡和自噬,在这种情况下有利于组织修复。此外,mTOR与其他信号通路之间的关联可能在众多疾病的病理生理学中起关键作用。mTOR与NF-κB、Akt、PI3K、MAPK、GSK-3β、Nrf2/HO-1、JAK/STAT、CREB/BDNF和ERK1/2通路紧密相关,它们共同在不同身体器官的炎症、凋亡、细胞存活和氧化应激调节中发挥重要作用。研究表明,抑制mTOR可能有益于治疗代谢、神经和心血管疾病,以及可能延长预期寿命。因此,识别能够调节mTOR信号通路的新化学物质和药物有望用于治疗和预防这些疾病。姜黄素就是这样一种对mTOR通路具有调节作用的药物,使其成为通过靶向mTOR来减少复杂疾病相关并发症的令人兴奋的选择。本综述旨在探讨姜黄素调节mTOR信号通路的潜力及其治疗意义。