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

Inflammation in multiple sclerosis (MS). Immune T-cells bypassing the blood-brain barrier (BBB) affect oligodendrocyte structure and activate glial response through NF-κB and AP-1. Reactive oxygen species (ROS) and nitric oxide (NO) secretion by activated microglia and astrocytes further contribute to myelin damage, axon degradation, and ultimate neuronal death.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Inflammation in multiple sclerosis (MS). Immune T-cells bypassing the blood-brain barrier (BBB) affect oligodendrocyte structure and activate glial response through NF-κB and AP-1. Reactive oxygen species (ROS) and nitric oxide (NO) secretion by activated microglia and astrocytes further contribute to myelin damage, axon degradation, and ultimate neuronal death.

Mentions: MS is an inflammatory disease in which the insulating myelin of SNC is damaged (Duncan and Heales, 2005). Of unknown etiology, this disease is characterized by an infiltration of inflammatory mononuclear cells into the CNS through a damaged blood-brain barrier (BBB), which causes the release of inflammatory and cytotoxic mediators, including NO (Smith and Lassmann, 2002). This neuroinflammation elicits the infiltration of T lymphocytes, the recruitment of macrophages, astrocytic damage and the local activation of microglia (Gay et al., 1997; Nikić et al., 2011). Although there is a strong correlation between neuroinflammation and axonal damage, the exact mechanism of this damage has to be elucidated (Figure 5).


Implications of glial nitric oxide in neurodegenerative diseases.

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

Inflammation in multiple sclerosis (MS). Immune T-cells bypassing the blood-brain barrier (BBB) affect oligodendrocyte structure and activate glial response through NF-κB and AP-1. Reactive oxygen species (ROS) and nitric oxide (NO) secretion by activated microglia and astrocytes further contribute to myelin damage, axon degradation, and ultimate neuronal death.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Inflammation in multiple sclerosis (MS). Immune T-cells bypassing the blood-brain barrier (BBB) affect oligodendrocyte structure and activate glial response through NF-κB and AP-1. Reactive oxygen species (ROS) and nitric oxide (NO) secretion by activated microglia and astrocytes further contribute to myelin damage, axon degradation, and ultimate neuronal death.
Mentions: MS is an inflammatory disease in which the insulating myelin of SNC is damaged (Duncan and Heales, 2005). Of unknown etiology, this disease is characterized by an infiltration of inflammatory mononuclear cells into the CNS through a damaged blood-brain barrier (BBB), which causes the release of inflammatory and cytotoxic mediators, including NO (Smith and Lassmann, 2002). This neuroinflammation elicits the infiltration of T lymphocytes, the recruitment of macrophages, astrocytic damage and the local activation of microglia (Gay et al., 1997; Nikić et al., 2011). Although there is a strong correlation between neuroinflammation and axonal damage, the exact mechanism of this damage has to be elucidated (Figure 5).

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