The expanding roles of neuronal nitric oxide synthase (NOS1)

Abstract

The nitric oxide synthases (NOS; EC 1.14.13.39) use L-arginine as a substrate to produce nitric oxide (NO) as a by-product in the tissue microenvironment. NOS1 represents the predominant NO-producing enzyme highly enriched in the brain and known to mediate multiple functions, ranging from learning and memory development to maintaining synaptic plasticity and neuronal development, Alzheimer’s disease (AD), psychiatric disorders and behavioral deficits. However, accumulating evidence indicate both canonical and non-canonical roles of NOS1-derived NO in several other tissues and chronic diseases. A better understanding of NOS1-derived NO signaling, and identification and characterization of NO-metabolites in non-neuronal tissues could become useful in diagnosis and prognosis of diseases associated with NOS1 expression. Continued investigation on the roles of NOS1, therefore, will synthesize new knowledge and aid in the discovery of small molecules which could be used to titrate the activities of NOS1-derived NO signaling and NO-metabolites. Here, we address the significance of NOS1 and its byproduct NO in modifying pathophysiological events, which could be beneficial in understanding both the disease mechanisms and therapeutics.

CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain

“…Methionyl-tRNA formyl transferase (MTFMT) instrumental in regulating mitochondrial function to mediate innate defense against infection was increased (77). Nitric oxide synthase (NOS1), associated with AD, psychiatric disorders, and behavioral deficits (78) also displayed increased expression. An increase in Lysine methyltransferase 2A (KMT2A), which plays a critical role in monocyte and macrophage inflammation, was also noted (79).…”

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“…As its chemistry shows high reactivity, the amount of NO produced and its location significantly influence the signalizing message. NOSI and NOSIII produce a low output of NO and are dependent on Ca 2+ activation, whereas NOS II produces a high output of NO independent of Ca 2+ . , NOS I and III are constitutive enzymes that produce NO for body homeostasis. NOS I was first discovered in neurons, and has a well-established role in producing NO for multiple functions in the brain, including learning to maintain synaptic plasticity. , NOS III was originally discovered in endothelial cells and contributes to the production of NO in blood vessels, assisting in the regulation of vascular tone and blood pressure, among other functions .…”

“…NOSI and NOSIII produce a low output of NO and are dependent on Ca 2+ activation, whereas NOS II produces a high output of NO independent of Ca 2+ . , NOS I and III are constitutive enzymes that produce NO for body homeostasis. NOS I was first discovered in neurons, and has a well-established role in producing NO for multiple functions in the brain, including learning to maintain synaptic plasticity. , NOS III was originally discovered in endothelial cells and contributes to the production of NO in blood vessels, assisting in the regulation of vascular tone and blood pressure, among other functions . NOS II was first found in cytokine-induced macrophages and is a Ca 2+ -independent enzyme that produces a high amount of NO, with toxic effects related to antimicrobial, antiparasitic, and antineoplastic activities. ,,, …”

“…NOSI and NOSIII produce a low output of NO and are dependent on Ca 2+ activation, whereas NOS II produces a high output of NO independent of Ca 2+ . 19,20 NOS I and III are constitutive enzymes that produce NO for body homeostasis. NOS I was first discovered in neurons, and has a wellestablished role in producing NO for multiple functions in the brain, including learning to maintain synaptic plasticity.…”

“…21 NOS II was first found in cytokine-induced macrophages and is a Ca 2+ -independent enzyme that produces a high amount of NO, with toxic effects related to antimicrobial, antiparasitic, and antineoplastic activities. 16,19,20,22 Overexpression or dysregulation of NOS expression has been linked to several pathologies, prompting research efforts to develop iNOS inhibitors. While these inhibitors have demonstrated promising results in animal studies, their effectiveness has not been successfully translated to humans.…”