Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2024 Aug 17;51(1):913. doi: 10.1007/s11033-024-09862-2.
Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.
Klotho 被认为是一种衰老抑制蛋白，涉及多种过程和信号通路。Klotho 的抗炎、抗凋亡、抗氧化和抗肿瘤生物活性扩展了其在神经科学中的应用，并因其延长寿命的能力而使该蛋白广受欢迎。此外，已经证明 klotho 水平会随着衰老和许多病理过程而降低，特别是与中枢神经系统（CNS）相关的病理过程。有证据表明，klotho 可以成为中枢神经系统疾病（如肌萎缩侧索硬化症、帕金森病、中风和阿尔茨海默病）的关键治疗靶点。文献综述表明，klotho 表达的上调调节了与神经紊乱中的自噬、氧化应激、炎症、认知和铁死亡相关的各种信号通路。因此，开发能够提高或恢复 klotho 水平的药物或试剂引起了极大的兴趣。在这方面，本综述旨在收集有关 Klotho 在中枢神经系统疾病中的治疗潜力的相关文献，重点关注分子和细胞机制。
