Nitric Oxide Dynamics in Central Nervous System Disorders

Nitric oxide (NO) is a gaseous signalling molecule with a pivotal role in cerebrovascular regulation, synaptic modulation and innate immune responses within the central nervous system (CNS). Under physiological conditions, endothelial and neuronal nitric oxide synthases (eNOS and nNOS) generate low levels of NO to maintain vascular tone and support neuroplasticity. In contrast, during neuroinflammatory or neurodegenerative states, inducible nitric oxide synthase (iNOS) in microglia and infiltrating macrophages produces high concentrations of NO and reactive nitrogen species, precipitating a cascade of nitrosative stress, mitochondrial dysfunction and protein modifications. Such dysregulation is implicated in multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease and acute injuries such as stroke. Temporal and spatial patterns of NO production determine whether signalling pathways confer neuroprotection or drive tissue damage. Advances in in vivo imaging and cerebrospinal fluid biomarkers have begun to resolve the complex dynamics of NO synthesis and downstream nitrosative modifications, offering new avenues for diagnosis and targeted intervention in CNS disorders.

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Nitric Oxide Dynamics in Central Nervous System Disorders publication trend

The graph below shows the total number of articles in nitric oxide dynamics in central nervous system disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Inducible nitric oxide synthase (iNOS): Enzyme upregulated in activated microglia and macrophages that produces high levels of NO during inflammation.

Nitrosative stress: Cellular damage arising from excessive reactive nitrogen species, including peroxynitrite, leading to lipid peroxidation and protein oxidation.

S-nitrosylation: Post-translational modification in which an NO moiety is covalently attached to a cysteine thiol, altering protein function.

Nitrite/nitrate (NOx): Stable oxidation products of NO used as surrogate biomarkers to quantify systemic or central nitrosative activity.

Experimental autoimmune encephalomyelitis (EAE): Animal model of CNS demyelination and neuroinflammation that recapitulates key features of multiple sclerosis.

References

1. The Use of Nitrosative Stress Molecules as Potential Diagnostic Biomarkers in Multiple Sclerosis. International Journal of Molecular Sciences (2024).
2. Inducible nitric oxide synthase deficiency promotes murine-β-coronavirus induced demyelination. Virology Journal (2023).
3. Therapeutic potential of blocking GAPDH nitrosylation with CGP3466b in experimental autoimmune encephalomyelitis. Frontiers in Neurology (2023).