Emerging roles of nitric oxide in neurodegeneration

Chung, Kenny K.K.; David, Karen K.

doi:10.1016/j.niox.2010.02.002

Cited by 48 publications

(38 citation statements)

References 74 publications

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“…Neuronal NO is a signaling molecule which functions in a wide variety of physiologic and pathophysiologic processes such as neurotransmission, neuroprotection, and neurotoxicity 11 . In the urogenital system, nNOS production of NO within CN fibers supplying the penis is well-established as the primary stimulus for neuronally induced penile erection 4 .…”

Section: Discussionmentioning

confidence: 99%

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Neuronal Nitric Oxide Signaling Regulates Erection Recovery After Cavernous Nerve Injury

2012

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Purpose NO is the major neuronal mediator of penile erection, but its role in EF status after CN injury is uncertain. This study aimed to determine the function of neuronal NO signaling in the pathobiology of EF recovery after partial CN injury using both genetic and pharmacologic mouse experimental paradigms. Materials and Methods EF was evaluated in WT and nNOS−/− mice (n=5–7/group) at 1, 3 and 7 days after UCI or sham injury and at day 7 in WT mice treated with the NO synthase inhibitor, L-NAME at baseline and for 6 days following UCI. Apoptosis in the penis was evaluated by Western blot analysis of p-Akt-S473, 3-NT, and caspase-3 expressions after BCI. Results ICP was significantly decreased at 1, 3 and 7 days in WT mice but only at day 1 in nNOS−/− mice after UCI compared with sham treatment values (p<0.05). L-NAME-treated WT mice had improved EF compared with the vehicle-treated group response at day 7 following UCI (p<0.05). p-Akt-S473 expression in penes was significantly decreased in vehicle-treated (p<0.05) but not L-NAME-treated WT mice. 3-NT expression in penes was significantly decreased in L-NAME-treated WT and vehicle-treated nNOS−/− mice (p<0.05). Caspase-3 expression in penes was significantly increased in vehicle-treated (p<0.05) but not L-NAME-treated WT mice and vehicle-treated nNOS−/− mice. Conclusions Neuronal NO signaling regulates EF recovery early after partial CN injury, exerting an inhibitory role via induction of apoptotic changes in penile tissue. Therapeutic strategies to improve EF recovery after RP may consider targeting pathogenic sites of NO neurobiology.

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Section: Discussionmentioning

confidence: 99%

“…In addition to its well characterized role in physiologic cellular signaling, NO is characterized to mediate pathological conditions 11 . NO can cause cytotoxicity by reacting with superoxide radicals to produce a potent oxidant peroxynitrite.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Signaling Regulates Erection Recovery After Cavernous Nerve Injury

2012

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“…Excessive NO is toxic to neurons, 139 where it condenses with superoxide to form peroxynitrite, 112 a powerful oxidant that irreversibly damages lipids, DNA, carbohydrates, and proteins, leading to mitochondrial dysfunction and cellular degeneration. [141][142][143][144][145] This nitrative damage occurs early in the progression of AD and may be important for transition from mild cognitive impairment to the severe impairment characteristic of AD. 146 To examine empirically the association of AD and NO overproduction, we measured the stable NO metabolites, nitrite and nitrate, in rat brain with experimental AD.…”

Section: Intermittent Hypoxic Training (Iht) Improves Cerebrovascularmentioning

confidence: 99%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

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“…As the metabolic activity of brain is relatively high, the aberrant electron transfers result in additional free radical formation and subsequent protein nitration in aged brain tissue. Therefore, protein nitration is generally considered as a biomarker for age-related neurodegeneration (Butterfield et al, 2006;Chung and David, 2010). Moreover, nitroxidative damage of neurons can also contribute to age-related deficits in memory function.…”

Section: Fig 1 Protein Nitration and Its Consequencesmentioning

confidence: 99%