Implications of glial nitric oxide in neurodegenerative diseases

Abstract

Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases.

Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders

“…MVB = multivesicular body proinflammatory cytokines released from microglia, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α [67]. Microgliosis, astrogliosis, and peripheral immune infiltration contribute to the cognitive and motor deficits, and lead to a toxic increase in the levels of reactive oxygen species [68], and to secondary neurodegeneration, characteristic of late disease stages [69]. Immunotherapy has been shown to induce a physiological microglial response (M2 type) and reduce the production of proinflammatory cytokines [65,66], thus exerting an anti-inflammatory effect in neurodegenerative disorders [70,71].…”

Role of nitric oxide in the regulation of immune responses during rabies virus infection in mice

“…Prolonged survival time was correlated with reduced viral load, which was evident by real-time PCR, reduced fluorescent and IHC signals in brain, suggesting the role of NO in rabies virus replication. NO has been reported to be involved in the pathogenesis of neurodegenerative diseases by damaging the BBB [22,38]. CVS strain of fixed RABV in suckling, neonatal and adult mice produces encephalitis with marked neuronal apoptosis in various regions of brain when inoculated intracerebrally [15,16].…”

“…Nitric oxide has been reported to be involved in pathogenesis of neurodegenerative diseases, including rabies [22]. Reduced state of NO (NO -) in RABV infected brains [17], reacted with superoxide (O 2 -) to form peroxynitrate, which damage BBB by lipid peroxidation [22,23].…”

“…Reduced state of NO (NO -) in RABV infected brains [17], reacted with superoxide (O 2 -) to form peroxynitrate, which damage BBB by lipid peroxidation [22,23].…”

Remarkably Strong Chemisorption of Nitric Oxide on Insulating Oxide Films Promoted by Hybrid Structure

“…The discovery of bioregulatory functions of nitric oxide is astounding and revised scientists' understanding of how cells communicate and defend themselves 6 . Nitric oxide can serve as messenger (signaling molecule) in biological processes in immune and nervous systems at low concentration [7][8][9][10][11][12] . As a by-product of high temperature combustion and exhaust gases generated by motor cars, this colorless gas is one of most common and primary air pollutants.…”