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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

Glial-induced neuroinflammation and neurotoxicity in amyotrophic lateral sclerosis (ALS). Reactive astrocytes contribute to the degenerative process by influencing the activity of microglial and immune cells. An up-regulation of filament glial fibrillary acidic protein (GFAP) takes place and astrocytes increase the release of proinflammatory markers including NO and ROS. When mutated SOD1 accumulates within microglia, the later generates substances potentially harmful to other cells, thus potentiating neurotoxicity. Demyelinization and progressive loss of cholesterol is also observed after oligodendrocyte damage. These glial cells show a reduction in the monocarboxylate transporter 1 (MCT1), which in turn difficult the energy supplies to the neuron.
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Figure 6: Glial-induced neuroinflammation and neurotoxicity in amyotrophic lateral sclerosis (ALS). Reactive astrocytes contribute to the degenerative process by influencing the activity of microglial and immune cells. An up-regulation of filament glial fibrillary acidic protein (GFAP) takes place and astrocytes increase the release of proinflammatory markers including NO and ROS. When mutated SOD1 accumulates within microglia, the later generates substances potentially harmful to other cells, thus potentiating neurotoxicity. Demyelinization and progressive loss of cholesterol is also observed after oligodendrocyte damage. These glial cells show a reduction in the monocarboxylate transporter 1 (MCT1), which in turn difficult the energy supplies to the neuron.

Mentions: Together, all these data support the idea of a prominent role of oxidative harm as one of the principal cellular mechanisms of motor neuron degeneration (Beckman and Esteves, 2006; Figure 6).


Implications of glial nitric oxide in neurodegenerative diseases.

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

Glial-induced neuroinflammation and neurotoxicity in amyotrophic lateral sclerosis (ALS). Reactive astrocytes contribute to the degenerative process by influencing the activity of microglial and immune cells. An up-regulation of filament glial fibrillary acidic protein (GFAP) takes place and astrocytes increase the release of proinflammatory markers including NO and ROS. When mutated SOD1 accumulates within microglia, the later generates substances potentially harmful to other cells, thus potentiating neurotoxicity. Demyelinization and progressive loss of cholesterol is also observed after oligodendrocyte damage. These glial cells show a reduction in the monocarboxylate transporter 1 (MCT1), which in turn difficult the energy supplies to the neuron.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Glial-induced neuroinflammation and neurotoxicity in amyotrophic lateral sclerosis (ALS). Reactive astrocytes contribute to the degenerative process by influencing the activity of microglial and immune cells. An up-regulation of filament glial fibrillary acidic protein (GFAP) takes place and astrocytes increase the release of proinflammatory markers including NO and ROS. When mutated SOD1 accumulates within microglia, the later generates substances potentially harmful to other cells, thus potentiating neurotoxicity. Demyelinization and progressive loss of cholesterol is also observed after oligodendrocyte damage. These glial cells show a reduction in the monocarboxylate transporter 1 (MCT1), which in turn difficult the energy supplies to the neuron.
Mentions: Together, all these data support the idea of a prominent role of oxidative harm as one of the principal cellular mechanisms of motor neuron degeneration (Beckman and Esteves, 2006; Figure 6).

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