Roles of Nitric Oxide Synthase Isoforms in Neurogenesis

Abstract

Nitric oxide (NO), a free radical gas, acts as a neurotransmitter or neuromodulator in the central nervous system (CNS). It has been widely explored as a mediator of neuroinflammation, neuronal damages, and neurodegeneration at its pathological levels. Recently, increasing evidence suggests that NO plays key roles in mediating adult neurogenesis, the process of neural stem cells (NSCs) to generate newborn neurons for replacing damaged neurons or maintaining the function of the brain. NO synthase (NOS) is a major enzyme catalyzing the generation of NO in the brain. Recent studies indicate that three homologous NOS isoforms are involved in the proliferation of NSCs and neurogenesis. Therefore, the impact of NOS isoforms on NSC functions needs to be elucidated. Here, we summarize the studies on the role of NO and NOS with different isoforms in NSC proliferation and neurogenesis with the focus on introducing action mechanisms involved in the regulation of NSC function. This growing research area provides the new insight into controlling NSC function via regulating NO microenvironment in the brain. It also provides the evidence on targeting NOS for the treatment of brain diseases.

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

“…As such, 3DG can become a good drug carrier for those diseases due to its extra capacity to induce this enzyme's expression. Nitric oxide synthase is an oxidoreductase involved in various biological processes such as neurotransmission, amino acid metabolism, environmental signaling pathways, catabolism (Li et al, 2007;Naglah et al, 2016), the endocrine system, and smooth muscle motor control (Adams and Bronner-Fraser, 2009;Hillard, 2015), neuronal damages, neurodegeneration, and NSCs proliferation (Chong et al, 2018). L-amino acid oxidase is involved in the biosynthesis and metabolism of amino acids (Niedermann and Lerch, 1991), and we found that 3DG causes down-regulation of this enzyme in NSCs.…”

Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

“…Growing empirical evidence indicates a unique role of NO in adult neurogenesis [70]. Accordingly, several agents have been successfully trialed with a rationale to increase brain NO levels, including arginine [71] and NO-donor supplementation [6].…”

Cysteines as Redox Molecular Switches and Targets of Disease

“…NO is produced in the brain by neuronal NO synthase (nNOS) and serves as a key second messenger for instance, regulating neuronal plasticity and survival (Nakamura and Lipton, 2016; Chong et al, 2017). However, aberrant S-nitrosylation of proteins such as PDI and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) can occur in AD (Uehara et al, 2006; Zhao et al, 2015).…”