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Implications of glial nitric oxide in neurodegenerative diseases.

Yuste JE, Tarragon E, Campuzano CM, Ros-Bernal F - Front Cell Neurosci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Neurobiotechnology Group, Departament of Medicine, Facultat de Ciències de la Salut, Universitat Jaume I Castelló de la Plana, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

Neuroinflammation in Parkinson’s disease (PD). Different genetic and/or environmental factors such as parkin mutations or MTPT exposure lead to the accumulation of α-synuclein aggregates in the brain. This accumulation triggers the activation of glial cells. The proinflammatory cytokines freed by astrocytes and microglia stimulate the release of several neuroinflammatory markers, including NO, IL-6, IL-1β, and TNF-α, which can promote neuronal death and aggravate the neurodegenerative process.
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Figure 4: Neuroinflammation in Parkinson’s disease (PD). Different genetic and/or environmental factors such as parkin mutations or MTPT exposure lead to the accumulation of α-synuclein aggregates in the brain. This accumulation triggers the activation of glial cells. The proinflammatory cytokines freed by astrocytes and microglia stimulate the release of several neuroinflammatory markers, including NO, IL-6, IL-1β, and TNF-α, which can promote neuronal death and aggravate the neurodegenerative process.

Mentions: A potential role of NO and NOS isoforms in the pathophysiology of PD has been emphasized. Increases in iNOS expression and NO-mediated modulation of the mitochondrial apoptotic pathway have also been observed after injection of lipopolysaccharide (LPS) or 6-OHDA in the SN and striatum in different experimental models of PD (Singh et al., 2005). It is worth mentioning that nNOS overexpression and the formation of peroxynitrite in polymorphonuclear leukocytes have been reported in PD patients (Gatto et al., 2000; Gilgun-Sherki et al., 2001). Interestingly, this peroxynitrite exposure has been also linked to the formation of α-synuclein aggregates (Souza et al., 2000). This is important, given that nitrated α-synuclein seems to contribute to the increased ROS production, decreased adenosine triphosphate (ATP) production, and degeneration of dopaminergic neurons, as well as to microglial activation, a reduction in the number of T-cells and increased cell death (Murray et al., 2003; Guix et al., 2005; Figure 4).


Implications of glial nitric oxide in neurodegenerative diseases.

Yuste JE, Tarragon E, Campuzano CM, Ros-Bernal F - Front Cell Neurosci (2015)

Neuroinflammation in Parkinson’s disease (PD). Different genetic and/or environmental factors such as parkin mutations or MTPT exposure lead to the accumulation of α-synuclein aggregates in the brain. This accumulation triggers the activation of glial cells. The proinflammatory cytokines freed by astrocytes and microglia stimulate the release of several neuroinflammatory markers, including NO, IL-6, IL-1β, and TNF-α, which can promote neuronal death and aggravate the neurodegenerative process.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4538301&req=5

Figure 4: Neuroinflammation in Parkinson’s disease (PD). Different genetic and/or environmental factors such as parkin mutations or MTPT exposure lead to the accumulation of α-synuclein aggregates in the brain. This accumulation triggers the activation of glial cells. The proinflammatory cytokines freed by astrocytes and microglia stimulate the release of several neuroinflammatory markers, including NO, IL-6, IL-1β, and TNF-α, which can promote neuronal death and aggravate the neurodegenerative process.
Mentions: A potential role of NO and NOS isoforms in the pathophysiology of PD has been emphasized. Increases in iNOS expression and NO-mediated modulation of the mitochondrial apoptotic pathway have also been observed after injection of lipopolysaccharide (LPS) or 6-OHDA in the SN and striatum in different experimental models of PD (Singh et al., 2005). It is worth mentioning that nNOS overexpression and the formation of peroxynitrite in polymorphonuclear leukocytes have been reported in PD patients (Gatto et al., 2000; Gilgun-Sherki et al., 2001). Interestingly, this peroxynitrite exposure has been also linked to the formation of α-synuclein aggregates (Souza et al., 2000). This is important, given that nitrated α-synuclein seems to contribute to the increased ROS production, decreased adenosine triphosphate (ATP) production, and degeneration of dopaminergic neurons, as well as to microglial activation, a reduction in the number of T-cells and increased cell death (Murray et al., 2003; Guix et al., 2005; Figure 4).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Neurobiotechnology Group, Departament of Medicine, Facultat de Ciències de la Salut, Universitat Jaume I Castelló de la Plana, Spain.

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.

No MeSH data available.


Related in: MedlinePlus