Role of nitric oxide in neurodegenerative diseases.
Role of nitric oxide in neurodegenerative diseases.
复制标题
一氧化氮在神经退行性疾病中的作用。
DOI：
10.1097/00019052-199512000-00016
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发表时间：
1995
影响因子：
4.8
通讯作者：
Beal,MF
中科院分区：
文献类型：
--
作者：
Schulz,JB;Matthews,RT;Beal,MF
除了作为多种生理功能介质的作用外，一氧化氮在过量产生的条件下似乎是一种神经毒素，这表明一氧化氮在神经退行性疾病中的作用。越来越多的证据表明兴奋性毒性是急性和慢性神经系统疾病中细胞死亡的机制。兴奋性氨基酸受体的激活通过细胞内钙浓度的增加导致神经元一氧化氮合酶的激活。一氧化氮可能抑制能量代谢的关键酶、损伤DNA、消耗细胞内谷胱甘肽，并与超氧化物反应形成过氧亚硝酸盐。后者是一种高反应性分子，一种强效氧化剂，已知可引发脂质过氧化、芳香族氨基酸残基的羟基化和硝化以及蛋白质的硫氢基氧化，并分解为二氧化氮和具有类羟基反应性的物质。现在有证据表明一氧化氮的神经元产生和过氧亚硝酸盐的形成发生在体内。
Besides its role as a mediator of several physiological functions, nitric oxide appears to be a neurotoxin under conditions of excessive production, which suggests a role for nitric oxide in neurodegenerative diseases. An increasing body of evidence has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurologic diseases. Activation of excitatory amino acid receptors leads to activation of neuronal nitric oxide synthase by an increase in intracellular calcium concentrations. Nitric oxide may inhibit key enzymes of energy metabolism, damage DNA, deplete intracellular glutathione, and react with superoxide to form peroxynitrite. The latter is a highly reactive molecule, a potent oxidizing agent known to initiate lipid peroxidation, hydroxylation and nitration of aromatic amino acid residues, and sulfhydryl oxidation of proteins, and to decompose to nitrogen dioxide and species with hydroxyl-like reactivity. There now is evidence that the neuronal production of nitric oxide and the formation of peroxynitrite occurs in vivo.