Research progress on neurobiology of neuronal nitric oxide synthase

被引:45
作者
Luo, Chun-Xia [1 ]
Zhu, Dong-Ya [1 ]
机构
[1] Nanjing Med Univ, Lab Cerebrovasc Dis, Sch Pharm, Dept Pharmacol, Nanjing 210029, Peoples R China
基金
中国国家自然科学基金;
关键词
neuronal nitric oxide synthase; cAMP response element-binding protein; post-synaptic density protein 95; synaptogenesis; neurogenesis; LONG-TERM POTENTIATION; FOCAL CEREBRAL-ISCHEMIA; AMYOTROPHIC-LATERAL-SCLEROSIS; MOUSE SUBVENTRICULAR ZONE; TRANSIENT GLOBAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; ADULT DENTATE GYRUS; NEURAL STEM-CELLS; ALZHEIMERS-DISEASE; HIPPOCAMPAL NEUROGENESIS;
D O I
10.1007/s12264-011-1038-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons, to some extent in astrocytes and neuronal stem cells. The alternative splicing of nNOS mRNA generates 5 isoforms of nNOS, including nNOS-alpha, nNOS-beta, nNOS-mu, nNOS-gamma and nNOS-2. Monomer of nNOS is inactive, and dimer is the active form. Dimerization requires tetrahydrobiopterin (BH4), heme and L-arginine binding. Regulation of nNOS expression relies largely on cAMP response element-binding protein (CREB) activity, and nNOS activity is regulated by heat shock protein 90 (HSP90)/HSP70, calmodulin (CaM), phosphorylation and dephosphorylation at Ser847 and Ser1412, and the protein inhibitor of nNOS (PIN). There are primarily 9 nNOS- interacting proteins, including post-synaptic density protein 95 (PSD95), clathrin assembly lymphoid leukemia (CALM), calcium/calmodulin-dependent protein kinase II alpha (CAMKIIA), Disks large homolog 4 (DLG4), DLG2, 6-phosphofructokinase, muscle type (PFK-M), carboxy-terminal PDZ ligand of nNOS (CAPON) protein, syntrophin and dynein light chain (LC). Among them, PSD95, CAPON and PFK-M are important nNOS adapter proteins in neurons. The interaction of PSD95 with nNOS controls synapse formation and is implicated in N-methyl-D-aspartic acid-induced neuronal death. nNOS- derived NO is implicated in synapse loss-mediated early cognitive/motor deficits in several neuropathological states, and negatively regulates neurogenesis under physiological and pathological conditions.
引用
收藏
页码:23 / 35
页数:13
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