Limits...
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

Central role of amyloid β-peptide (Aβ) in the oxidative stress elements involved in Alzheimer’s disease (AD). Accumulation of Aβ plaques results in oxidative stress. This oxidative stress might result from the implication of different pathways, such as mithocondrial dysfunction or inflammatory response, and it is manifested by synaptic damage and alterations in Ca2+ homeostasis. This may lead to apoptotic processes that result in the death of the cell and neurotoxicity. This is consistent with the concept of Aβ-associated oxidative stress and neurodegeneration in AD brain.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4538301&req=5

Figure 3: Central role of amyloid β-peptide (Aβ) in the oxidative stress elements involved in Alzheimer’s disease (AD). Accumulation of Aβ plaques results in oxidative stress. This oxidative stress might result from the implication of different pathways, such as mithocondrial dysfunction or inflammatory response, and it is manifested by synaptic damage and alterations in Ca2+ homeostasis. This may lead to apoptotic processes that result in the death of the cell and neurotoxicity. This is consistent with the concept of Aβ-associated oxidative stress and neurodegeneration in AD brain.

Mentions: The imbalance produced by the detoxification of ROS prompts an increase in oxidative stress that has proved to be involved in several excitotoxicity processes (Ferrer et al., 2010). S-nitrosylation has also been implicated in AD (Lipton et al., 1993), exhibiting a modulatory effect on glutamatergic NMDA receptors (Lipton, 2007b). Over-stimulation of NMDA receptors may produce an excessive Ca2+ influx that can generate ROS and activate excitotoxicity processes that lead to cell death. Moreover, this excitotoxicity that has been suggested as a mediator of neurotoxicity in this neurodegenerative disorder (Lipton, 2007a), and specifically in neurons, may also activate nNOS and induce NO overproduction (Gu et al., 2010; Figure 3).


Implications of glial nitric oxide in neurodegenerative diseases.

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

Central role of amyloid β-peptide (Aβ) in the oxidative stress elements involved in Alzheimer’s disease (AD). Accumulation of Aβ plaques results in oxidative stress. This oxidative stress might result from the implication of different pathways, such as mithocondrial dysfunction or inflammatory response, and it is manifested by synaptic damage and alterations in Ca2+ homeostasis. This may lead to apoptotic processes that result in the death of the cell and neurotoxicity. This is consistent with the concept of Aβ-associated oxidative stress and neurodegeneration in AD brain.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Central role of amyloid β-peptide (Aβ) in the oxidative stress elements involved in Alzheimer’s disease (AD). Accumulation of Aβ plaques results in oxidative stress. This oxidative stress might result from the implication of different pathways, such as mithocondrial dysfunction or inflammatory response, and it is manifested by synaptic damage and alterations in Ca2+ homeostasis. This may lead to apoptotic processes that result in the death of the cell and neurotoxicity. This is consistent with the concept of Aβ-associated oxidative stress and neurodegeneration in AD brain.
Mentions: The imbalance produced by the detoxification of ROS prompts an increase in oxidative stress that has proved to be involved in several excitotoxicity processes (Ferrer et al., 2010). S-nitrosylation has also been implicated in AD (Lipton et al., 1993), exhibiting a modulatory effect on glutamatergic NMDA receptors (Lipton, 2007b). Over-stimulation of NMDA receptors may produce an excessive Ca2+ influx that can generate ROS and activate excitotoxicity processes that lead to cell death. Moreover, this excitotoxicity that has been suggested as a mediator of neurotoxicity in this neurodegenerative disorder (Lipton, 2007a), and specifically in neurons, may also activate nNOS and induce NO overproduction (Gu et al., 2010; Figure 3).

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