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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

Mechanisms through which ROS/RNS cause apoptosis. NO can induce oxidative and nitrosative stress, which activates mitochondrial apoptosis by several pathways, including: (i) stimulation of mitochondrial permeability transition (MPT); (ii) up-regulation of p53; (iii) activation of the p38 MAP kinase pathway; and (iv) induction of endoplasmic reticulum stress (ERS). All these processes produce cytochrome c release and apoptosis.
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Figure 2: Mechanisms through which ROS/RNS cause apoptosis. NO can induce oxidative and nitrosative stress, which activates mitochondrial apoptosis by several pathways, including: (i) stimulation of mitochondrial permeability transition (MPT); (ii) up-regulation of p53; (iii) activation of the p38 MAP kinase pathway; and (iv) induction of endoplasmic reticulum stress (ERS). All these processes produce cytochrome c release and apoptosis.

Mentions: Neuroinflammation-induced cell death is often derived from the long-term impact caused by the increase of reactive oxygen and nitrogen species (RONS), which play a major role in eliciting apoptotic cell death through irreversible oxidative or nitrosative injury to neuronal elements (Nakagawa and Yokozawa, 2002). The brain is highly susceptible to oxidative stress due to its imbalance between an efficient antioxidant defense system and its capacity to generate oxidative species. As a matter of fact, the brain presents low levels of glutathione (GSH) and moderate activity of the antioxidant enzymes catalase, superoxide dismutases (SODs) and GSH peroxidase. On the contrary, the elevated levels of ascorbic acid, the high concentration of transition metals such as copper and iron, and the huge aerobic metabolism contribute to the generation of oxidative (ROS/RNS) species eliciting necrotic neuronal death (Figure 2).


Implications of glial nitric oxide in neurodegenerative diseases.

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

Mechanisms through which ROS/RNS cause apoptosis. NO can induce oxidative and nitrosative stress, which activates mitochondrial apoptosis by several pathways, including: (i) stimulation of mitochondrial permeability transition (MPT); (ii) up-regulation of p53; (iii) activation of the p38 MAP kinase pathway; and (iv) induction of endoplasmic reticulum stress (ERS). All these processes produce cytochrome c release and apoptosis.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Mechanisms through which ROS/RNS cause apoptosis. NO can induce oxidative and nitrosative stress, which activates mitochondrial apoptosis by several pathways, including: (i) stimulation of mitochondrial permeability transition (MPT); (ii) up-regulation of p53; (iii) activation of the p38 MAP kinase pathway; and (iv) induction of endoplasmic reticulum stress (ERS). All these processes produce cytochrome c release and apoptosis.
Mentions: Neuroinflammation-induced cell death is often derived from the long-term impact caused by the increase of reactive oxygen and nitrogen species (RONS), which play a major role in eliciting apoptotic cell death through irreversible oxidative or nitrosative injury to neuronal elements (Nakagawa and Yokozawa, 2002). The brain is highly susceptible to oxidative stress due to its imbalance between an efficient antioxidant defense system and its capacity to generate oxidative species. As a matter of fact, the brain presents low levels of glutathione (GSH) and moderate activity of the antioxidant enzymes catalase, superoxide dismutases (SODs) and GSH peroxidase. On the contrary, the elevated levels of ascorbic acid, the high concentration of transition metals such as copper and iron, and the huge aerobic metabolism contribute to the generation of oxidative (ROS/RNS) species eliciting necrotic neuronal death (Figure 2).

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