N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities.

N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities.
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DOI:
10.1002/brb3.208
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发表时间:
2014-03
期刊:
影响因子:
3.1
通讯作者:
Alexandrov, Andrei V.
Alexandrov, Andrei V.
中科院分区:
心理学4区
文献类型:
--
作者:
Shahripour, Reza Bavarsad;Harrigan, Mark R.;Alexandrov, Andrei V.

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越来越多的研究领域正在研究具有多种作用机制的药物对治疗神经系统疾病的益处。 N-乙酰半胱氨酸 (NAC) 被广泛认为是对乙酰氨基酚过量的解毒剂,目前正在用于治疗血管和非血管神经系统疾病。 NAC 作为抗氧化剂谷胱甘肽的前体,调节谷氨酸能、神经营养和炎症途径。迄今为止,大多数 NAC 研究都是在各种神经系统疾病的动物模型中进行的,只有少数研究在人类中完成。在精神病学领域,NAC 作为辅助治疗已在 20 多项临床试验中进行了测试;然而,这个主题超出了本次审查的范围。在此,我们讨论 NAC 的分子、细胞内和全身效应,重点关注其在神经退行性疾病中的潜在应用,包括脊髓小脑共济失调、帕金森病、迟发性运动障碍、Unverricht-Lundbor 型肌阵挛癫痫以及多发性硬化症、肌萎缩侧索硬化症和阿尔茨海默病。最后,我们回顾了 NAC 在促进脑外伤、脑缺血后恢复以及治疗蛛网膜下腔出血后脑血管痉挛方面的潜在应用。
There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage.
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