Say NO to Alzheimer's disease: the putative links between nitric oxide and dementia of the Alzheimer's type

Law, Angeline

doi:10.1016/s0165-0173(00)00051-5

Cited by 297 publications

(185 citation statements)

References 446 publications

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“…This is likely the case in all cerebrovascular pathologies accompanied with cerebral ischaemia, leading to glutamate-dependent overactivation of the NMDA receptor, and stimulation of the calcium-dependent NO synthase (NOS) with persistent release of NO. 3,27 Similar events have been proposed to occur in PD, multiple sclerosis, amyotrophic lateral sclerosis and Huntington disease. In the nervous system, the NO chemistry has proved responsible for positive or negative effects, depending on experimental conditions.…”

Section: Neurodegeneration Nitric Oxide (No) and Mitochondriasupporting

confidence: 54%

Neurodegeneration and energy metabolism: from chemistry to clinics

Blandini¹,

Braunewell

Manahan‐Vaughan

et al. 2004

Cell Death Differ

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Section: Neurodegeneration Nitric Oxide (No) and Mitochondriasupporting

confidence: 54%

Neurodegeneration and energy metabolism: from chemistry to clinics

Blandini¹,

Braunewell

Manahan‐Vaughan

et al. 2004

Cell Death Differ

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“…26 There is increasing evidence that NO may have a role in AD pathogenetic mechanisms, either as a neurotoxic or neuroprotective agent. 37 The ability of NO to exert cellular damage due to its reactive oxidative properties may be considered as a primary neurotoxic mechanism. On the other hand, NO is likely involved in neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

et al. 2007

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To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer's disease (AD), we have developed a customized microarray containing all the ORFs (n = 2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT-PCR. We also detected mRNA expression of all the other urea cycle enzymes in AD brains. Immunochemistry experiments revealed that the OTC expression was strictly restricted to vascular endothelial cells in brain. Furthermore, OTC activity was 880% increased in the CSF of probable AD cases compared with controls. We analysed the association of the OTC À389 G/A and À241 A/G promoter polymorphisms with the risk of developing AD. We observed that rare haplotypes may be associated with the risk of AD through a possible modulation of the methylation of the OTC promoter. In conclusion, our results suggest the involvement of a new pathway in AD brains involving the urea cycle.

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“…In addition to regulating cerebral vasoactivity, NO possesses various physiological roles. NO synthesis is activated in cerebrovascular disease by the release of glutamate combined with inhibition of glutamate removal, which leads to NMDA receptor overactivation and excess Ca 2+ influx [38] . It is believed that the toxic effects of NO result from the actions of its downstream metabolite, ONOO-, according to models implicating NO in neurodegeneration.…”

Section: Excitotoxicity and Oxidative Stressmentioning

confidence: 99%

Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

2009

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A pivotal role for excitotoxicity in neurodegenerative diseases is gaining increasingly more acceptance, but the underlying mechanisms through which it participates in neurodegeneration still need further investigation. Excessive activation of glutamate receptors by excitatory amino acids leads to a number of deleterious consequences, including impairment of calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition and secondary excitotoxicity. Recent studies implicate excitotoxicity in a variety of neuropathological conditions, suggesting that neurodegenerative diseases with distinct genetic etiologies may share excitotoxicity as a common pathogenic pathway. Thus, understanding the pathways involved in excitotoxicity is of critical importance for the future clinical treatment of many neurodegenerative diseases. This review discusses the current understanding of excitotoxic mechanisms and how they are involved in the pathogenesis of neurodegenerative diseases.

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Say NO to Alzheimer's disease: the putative links between nitric oxide and dementia of the Alzheimer's type

Cited by 297 publications

References 446 publications

Neurodegeneration and energy metabolism: from chemistry to clinics

Neurodegeneration and energy metabolism: from chemistry to clinics

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

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