Functional Roles of Neuronal Nitric Oxide Synthase in Neurodegenerative Diseases and Mood Disorders

Abstract

: Nitric oxide synthase (NOS) is well known for its involvement in the regulation of the nervous, cardiovascular, and immune systems. Neuronal NOS (nNOS) is the most characterized NOS among all the isoforms. It accounts for most of the production of nitric oxide (NO) in the ner- vous system required for synaptic transmission and neuroplasticity. Previous studies have described the localization of nNOS in specific brain regions of interest. There is substantial evidence in the literature suggesting that nNOS signaling has significant involvement in several disease pathologies. However, the association between brain nNOS expression profiles and disease remains largely unknown. In this review, we attempt to delineate the contribution of nNOS signaling in memory and mood disorders in order to achieve a better understanding of nNOS in disease modulation.

Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication

“…The Tau family microtubule-associated proteins 118 and STIM2 responsible for neuronal calcium homeostasis impairment 119 were MS1262-targeted components of module M7 MAPK signaling and metabolism that is highly associated with the rate of cognitive decline. Plasma glial fibrillary acidic protein, an astrocyte reactivity biomarkers for AD 120 and nitric oxide synthase 1 for synaptic transmission and neuroplasticity 121 were MS1262-targeted components of modules M5 postsynaptic density or M11 cell-ECM interaction, respectively, again, major modules strongly correlated to AD neuropathology and cognition. In addition, MS1262 reversed the phosphorylation of components of modules M29, glycosylation/ER, and M42, matrisome, that were correlated with AD endophenotypes, and elevated tau microtubule-binding domain peptide levels correlate with the other MS1262-affected components of M42 matrisome and M11 cell-ECM modules.…”

Caffeine consumption and interaction with ADORA2A, CYP1A2 and NOS1 variants do not influence age at onset of Machado-Joseph disease

“…Excess of NO may contribute to neurodegeneration in Parkinson's disease (PD) [18]. A recent review concluded that NOS signaling has signi cant involvement in several disease pathologies, including protection against PD [19]. NOS effects were related to caffeine consumption in a preclinical study [20], while caffeine suppresses the generation of NO in microglia [21].…”

“…Nitric oxide (NO) performs vital physiological functions in the nervous system under normal concentrations [18]. The neuronal isoform (nNOS) signaling has signi cant involvement in several neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease and HD [19]. Caffeine reduces the expression of NOS, including nNOS [20,21].…”

Medium-Chain Fatty Acids Rescue Motor Function and Neuromuscular Junction Degeneration in a Drosophila Model of Amyotrophic Lateral Sclerosis

“…NO is a small, gaseous molecule with multiple roles in the CNS that include regulation of synaptic function, neuromodulation and neuromuscular junction formation [71][72][73]. NO facilitates neuronal death and neurodegeneration through glutamate-mediated excitotoxicity and inhibition of mitochondrial function [74][75][76]. In ALS, NO-mediated toxicity promotes degeneration of motor neurones [77]; this effect is likely mediated by the NO-derived peroxynitrite formation and subsequent 3-nitrotyrosination of proteins which is increased in the CNS of people affected by either sporadic or genetic forms of ALS [78], and in transgenic mouse models [79].…”