Aberrant expression of NOS isoforms in Alzheimer’s disease is structurally related to nitrotyrosine formation

Lüth, Hans-Joachim; Münch, Gerald; Arendt, Thomas

doi:10.1016/s0006-8993(02)03280-8

Cited by 207 publications

(128 citation statements)

References 74 publications

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“…FernandezVizarra et al (40) have shown that neuronal NOS protein levels aberrantly increase in AD neurons, whereas neuronal NOS activity in brain lysates is reduced. Increased expression of endothelial NOS in AD is also observed, but is primarily localized to the dystrophic neurites and astrocytes that surround amyloid plaques (11,41). Our quantitative PCR data support the idea that changes in constitutive NOS isoforms are unlikely to adequately compensate for the genetic loss of iNOS.…”

Section: Discussionsupporting

confidence: 74%

See 1 more Smart Citation

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

Colton¹,

Vitek²,

Wink

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

120

103

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Section: Discussionsupporting

confidence: 74%

“…Although commonly localized to macrophagic immune cells, iNOS is observed primarily in neurons and astrocytes in AD (10)(11)(12). Footprints of NO's past presence include observation of nitrated proteins in AD brains, compared with normal age-matched brains (13), suggesting that NO plays a role in the disease process.…”

mentioning

confidence: 99%

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

Colton¹,

Vitek²,

Wink

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

120

103

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show abstract

“…The functional consequences of this decrease are not clear, but, interestingly, kalirin-7 associates with inducible nitric oxide synthase (iNOS) in the hippocampus resulting in the downregulation of its enzymatic activity [76,78]. These data are in line with the findings that iNOS levels and activity are increased in AD [79,80], suggesting that the decrease of kalirin-7 in patients with AD contributes to further augment iNOS activity and exacerbate AD pathology [76]. Kalirin-7 decrease may also have a critical causative role in dendritic spine pathology in AD.…”

Section: Kalirin-7mentioning

confidence: 56%

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Lefort

2015

Neurotherapeutics

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Alzheimer's disease (AD) is a monumental public health crisis with no effective cure or treatment. To date, therapeutic strategies have focused almost exclusively on upstream signaling events in the disease, namely on β-amyloid and amyloid precursor protein processing, and have, unfortunately, yielded few, if any, promising results. An alternative approach may be to target signaling events downstream of β-amyloid and even tau. However, with so many pathways already linked to the disease, understanding which ones are "drivers" versus "passengers" in the pathogenesis of the disease remains a tremendous challenge. Given the critical roles of Rho-guanosine triphosphatases (GTPases) in regulating the actin cytoskeleton and spine dynamics, and the strong association between spine abnormalities and cognition, it is not surprising that mutations in a number of genes involved in RhoGTPase signaling have been implicated in several brain disorders, including schizophrenia and autism. And now, there is mounting literature implicating Rho-GTPase signaling in AD pathogenesis as well. Here, I review this evidence, with a particular emphasis on the regulators of Rho-GTPase signaling, namely guanine nucleotide exchange factors and GTPaseactivating proteins. Several of these have been linked to various aspects of AD, and each offers a novel potential therapeutic target for AD.

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“…The nNOS is expressed in the neurons of the cerebellum, hypothalamus, striatum, cerebral cortex and hippocampus as well as in the astrocytes. In the brain of individuals with AD, nNOS is aberrantly expressed in vulnerable pyramidal cells, astrocytes and nerve cells 6,7 . In physiological concentrations, NO plays a neuroprotective role in the nervous system whereas, it promotes apoptosis and cell death in high concentrations through stimulating of the superoxide anion formation in the mitochondria 8 .…”

mentioning

confidence: 99%

Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole

Anaeigoudari

Shafei

Soukhtanloo

et al. 2015

Arq. Neuro-Psiquiatr.

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Inflammation and oxidative stress have important roles in memory impairment. The effect of 7-nitroindazole (7NI) on lipopolysaccharide (LPS)-induced memory impairment was investigated. Rats were used, divided into four groups that were treated as follows: (1) control (saline); (2) LPS; (3) 7NI-LPS; and (4) 7NI before passive avoidance (PA). In the LPS group, the latency for entering the dark compartment was shorter than in the controls (p < 0.01 and p < 0.001); while in the 7NI-LPS group, it was longer than in the LPS group (p < 0.01 and p < 0.001). Malondialdehyde (MDA) and nitric oxide (NO) metabolite concentrations in the brain tissues of the LPS group were higher than in the controls (p < 0.001 and p < 0.05); while in the 7NI-LPS group, they were lower than in the LPS group (p < 0.001 and p < 0.05, respectively). The thiol content in the brain of the LPS group was lower than in the controls (p < 0.001); while in the 7NI-LPS group, it was higher than in the LPS group (p < 0.001). It is suggested that brain tissue oxidative damage and NO elevation have a role in the deleterious effects of LPS on memory retention that are preventable using 7NI.

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Aberrant expression of NOS isoforms in Alzheimer’s disease is structurally related to nitrotyrosine formation

Cited by 207 publications

References 74 publications

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole

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