Behbahan Faculty of Medical Sciences, Behbahan, Iran.
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Cell Biochem Funct. 2022 Apr;40(3):232-247. doi: 10.1002/cbf.3692. Epub 2022 Mar 8.
Traumatic brain injury (TBI) is one of the most concerning health issues in which the normal brain function may be disrupted as a result of a blow, bump, or jolt to the head. Loss of consciousness, amnesia, focal neurological defects, alteration in mental state, and destructive diseases of the nervous system such as cognitive impairment, Parkinson's, and Alzheimer's disease. Parkinson's disease is a chronic progressive neurodegenerative disorder, characterized by the early loss of striatal dopaminergic neurons. TBI is a major risk factor for Parkinson's disease. Existing therapeutic approaches have not been often effective, indicating the necessity of discovering more efficient therapeutic targets. The mammalian target of rapamycin (mTOR) signaling pathway responds to different environmental cues to modulate a large number of cellular processes such as cell proliferation, survival, protein synthesis, autophagy, and cell metabolism. Moreover, mTOR has been reported to affect the regeneration of the injured nerves throughout the central nervous system (CNS). In this context, recent evaluations have revealed that mTOR inhibitors could be potential targets to defeat a group of neurological disorders, and thus, a number of clinical trials are investigating their efficacy in treating dementia, autism, epilepsy, stroke, and brain injury, as irritating neurological defects. The current review describes the interplay between mTOR signaling and major CNS-related disorders (esp. neurodegenerative diseases), as well as the mTOR signaling-TBI relationship. It also aims to discuss the promising therapeutic capacities of mTOR inhibitors during the TBI.
创伤性脑损伤 (TBI) 是最令人关注的健康问题之一,其正常的大脑功能可能因头部受到打击、碰撞或震荡而受到干扰。包括意识丧失、遗忘、局灶性神经缺陷、精神状态改变以及神经系统破坏性疾病,如认知障碍、帕金森病和阿尔茨海默病。帕金森病是一种慢性进行性神经退行性疾病,其特征是早期纹状体多巴胺能神经元丧失。TBI 是帕金森病的主要危险因素。现有的治疗方法并不经常有效,这表明需要发现更有效的治疗靶点。哺乳动物雷帕霉素靶蛋白 (mTOR) 信号通路对不同的环境线索作出反应,从而调节大量的细胞过程,如细胞增殖、存活、蛋白质合成、自噬和细胞代谢。此外,已有报道称 mTOR 会影响中枢神经系统 (CNS) 中受损神经的再生。在这种情况下,最近的评估表明,mTOR 抑制剂可能是治疗一组神经疾病的潜在靶点,因此,许多临床试验正在研究它们在治疗痴呆、自闭症、癫痫、中风和脑损伤等刺激性神经缺陷方面的疗效。本文综述了 mTOR 信号与主要与 CNS 相关的疾病(特别是神经退行性疾病)之间的相互作用,以及 mTOR 信号与 TBI 的关系。本文还旨在讨论 mTOR 抑制剂在 TBI 中的有前途的治疗潜力。