title: Research progress on neurobiology of neuronal nitric oxide synthase.
abstract: 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-α, nNOS-β, nNOS-µ, nNOS-γ 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Laboratory of Cerebrovascular Disease, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Luo
authors.forename: Dong-Ya
authors.initials: DY
authors.lastname: Zhu
mesh_terms: D000818:Animals; D006801:Humans; D009446:Neurobiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*
chemical_list: D052248:Nitric Oxide Synthase Type I