nNOS-mediated protein-protein interactions: promising targets for treating neurological and neuropsychiatric disorders.
nNOS-mediated protein-protein interactions: promising targets for treating neurological and neuropsychiatric disorders.
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nNOS 介导的蛋白质-蛋白质相互作用：治疗神经系统和神经精神疾病的有希望的靶标
DOI：
10.7555/jbr.34.20200108
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发表时间：
2020-12-10
影响因子：
2.3
通讯作者：
Zhu D
中科院分区：
文献类型：
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作者：
Gu Y;Zhu D
神经和神经精神障碍是全世界导致残疾的主要原因之一，影响着数十亿人的健康。一氧化氮(NO)是一种具有多种生物活性的游离气体，主要由脑内神经元型一氧化氮合酶(NNOS)氧化L-精氨酸产生。抑制nNOS有益于多种神经和神经精神障碍，包括中风、抑郁和焦虑障碍、创伤后应激障碍、帕金森氏病、阿尔茨海默病、慢性疼痛和药物成瘾。由于nNOS在学习记忆和突触可塑性中的重要作用，直接抑制nNOS可能会引起严重的副作用。重要的是，包括突触后密度95(PSD-95)、nNOS羧基末端PDZ配体(Capon)和5-羟色胺转运体(SERT)在内的几种蛋白质与nNOS的PSD/Disc-Large/ZO-1同源结构域(PDZ)的相互作用已经被证明影响脑内该酶的亚细胞分布和活性。因此，干扰nNOS介导的蛋白质-蛋白质相互作用(PPI)将是一种更好的手段，而不会导致不良影响。本文综述了nNOS介导的PPI参与神经和神经精神疾病的研究现状，以及针对PPIs的药物的发现，以期为神经和神经精神疾病的治疗提供新的靶点和新的治疗策略。
Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people. Nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS) in the brain. Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders, including stroke, depression and anxiety disorders, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, chronic pain, and drug addiction. Due to critical roles of nNOS in learning and memory and synaptic plasticity, direct inhibition of nNOS may cause severe side effects. Importantly, interactions of several proteins, including post-synaptic density 95 (PSD-95), carboxy-terminal PDZ ligand of nNOS (CAPON) and serotonin transporter (SERT), with the PSD/Disc-large/ZO-1 homologous (PDZ) domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain. Therefore, it will be a preferable means to interfere with nNOS-mediated protein-protein interactions (PPIs), which do not lead to undesirable effects. Herein, we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders, and the discovery of drugs targeting the PPIs, which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.
影响因子：
--
作者：
Dai Y;He Z;Sui R;Jiang Z;Ma S
通讯作者：
Ma S