Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Thatcher, Gregory R. J.; Bennett, Brian M.; Reynolds, James N.

doi:10.2174/1567205053585945

Cited by 49 publications

(40 citation statements)

References 205 publications

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“…Thatcher's team has also synthesized chimeras able to release NO [10][11][12]. GT 1061, an NO mimetic compound that contains an ancillary, synergistic pharmacophore, is being investigated as neuroprotective in patients with Alzheimer's disease [6].…”

Section: No-nsaids: Rationale and Structurementioning

confidence: 99%

NO-donating NSAIDs and cancer: An overview with a note on whether NO is required for their action

Rigas

Williams

2008

Nitric Oxide

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Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) consist of a conventional NSAID to which an NO-releasing moiety is attached covalently, often via a spacer molecule. NONSAIDs represent an emerging class of compounds with chemopreventive properties against a variety of cancers, demonstrated in preclinical models including cell culture systems and animal tumor models; their potential efficacy in humans has not been assessed. Their mechanism of action appears complex and involves the generation of reactive oxygen species, suppression of microsatellite instability in mismatch repair-deficient cells, and modulation of several signaling cascades that culminate in inhibited cell renewal and enhanced apoptosis. NO, long appreciated to be able to protect from and also promote cancer, is released form NO-NSAIDs and constitutes their defining property. Existing data are consistent with the notion that NO may mediate their anticancer effect. In addition there is evidence that long term administration of NO-donating compounds is not associated with increased incidence of colon cancer. Whether NO release is required for the anticancer effect of NO-NSAIDs has being questioned by recent data indicating that, at least in the case of NO-aspirin, the NO-releasing moiety may serve as a leaving group while the spacer actually being the moiety responsible for its pharmacological action. Regardless of mechanistic issues, these compounds promise to contribute to the control of cancer.

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Section: No-nsaids: Rationale and Structurementioning

confidence: 99%

NO-donating NSAIDs and cancer: An overview with a note on whether NO is required for their action

Rigas

Williams

2008

Nitric Oxide

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“…This result suggested a compensatory response to oxidative stress due to an increase in endogenous H2O2 production. Thus the elevated level of SOD in methanol extract treatment group predicts that I. tinctoria may contain free radical scavenging activity, which could exert a beneficial action against the pathological alteration caused by the presence of O2 -and OH (Thatcher et al, 2005).…”

Section: Discussionmentioning

confidence: 92%

Effect of Indigofera tinctoria on ?-amyloid (25-35) mediated Alzheimer’s disease in mice: Relationship to antioxidant activity

Balamurugan¹,

Muralidharan²

2010

Bangladesh J Pharmacol

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Research ArticleEffect of Indigofera tinctoria on β-amyloid (25-35) mediated Alzheimer's disease in mice: Relationship to anti-oxidant activity BJP IntroductionOxidative stress has been implicated as a major cause of neurotoxicity in a number of neurodegenerative disorders including Alzheimer's disease. Oxidative damage in Alzheimer's disease may be a direct result of amyloid beta (AP). Markers of oxidative DNA damage, including mitochondrial DNA damage, have been localized to amyloid plaque affected areas in the Alzheimer's disease brain (Mecocci et al., 1994); the generation of lipid peroxidation products and the lipo peroxidation of membranes is also noted in amyloid plaques (Matsuoka et al., 2001).The mechanism of AP mediated oxidative stress may be direct or indirect, functionality of mitochondrial electron transport chain (ETC) is particularly susceptible to inhibition by AP, which is a major source of reactive oxygen species (ROS) within the cell and may therefore represent an indirect source of oxidative stress. Alternatively, AP can cause neurotoxicity by direct production of ROS (Behl et al., 1992), the mechanism which is directly related to biometal dyshomeostasis as evident in the brain of Alzheimer's disease (Lovell et al., 1998). Cell culture studies have provided further support for AP-ROS production as a potential mechanism for AP mediated neurodegeneration (Huang et al., 1999). The constant assault of oxidative stress during the aging process contributes towards neurodegeneration in Alzheimer's disease (Bush, 2003).Indigofera tinctoria Linn (Fabaceae) is an evergreen shrub native to entire India, especially in Southern India (Santapav and Henry, 1994). The entire plant is a stimulant, alternative and purgative. It is used in the treatment of liver and spleen enlargements. Root of the plant is used to cure hepatitis and urinary complications. The dried whole plant is used in phobia, delusion and disturbed mental states (Khare, 2007; AbstractThe oxidative stress reducing effect of methanol extract of Indigofera tinctoria leaves (250 and 500 mg/kg) was investigated on β-amyloid (25-35) peptideinduced Alzheimer's disease in mice. All the anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxide and glutathione reductase) in brain were reduced significantly (p<0.001) in the β-amyloid peptide injected group, whereas lipid peroxidation was increased significantly (p<0.001). The reduced enzyme level were restored significantly (p<0.01; p<0.001) by the administration of extract at the tested dose levels. A significant (p<0.001) reduction in lipid peroxidation was observed in the groups of animals administered with extract. Histopathological sections of the hippocampal region showed the extent of neuronal loss and its restoration upon administration of extract. Treatment with extract at the tested doses moderately prevented the neuronal loss. Article Info

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“…Lukiw et al (2005) attributed the elevation of this pro-inflammatory cytokine to the induction of inflammatory genes by Al. Furthermore, Aβ deposition due to Al-intoxication has been found to be Aβ plaques are surrounded by activated astrocytes and microglia which contribute to Al neurotoxicity through the induction of inflammatory cytokines such as IL-1β and TNF-α (Thatcher et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

POSSIBLE THERAPEUTIC ROLE OF <I>JASONIA CANDICANS</I> AND <I>JASONIA MONTANA</I> EXTRACTS IN THE REGRESSION OF ALZHEIMERâS DISEASE IN EXPERIMENTAL MODEL

Ahmed¹,

Booles²,

Khalil³

et al. 2013

American Journal of Biochemistry and Biotechnology

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The present article aimed to investigate the potential role of the ethanolic extracts of the aerial parts of Jasonia candicans and Jasonia montana in management of Alzheimer's Disease (AD) in experimental model. Supplementation of drinking water AlCl 3 (0.3%) for 16 weeks induced AD in male rats with siginifcant increase in brain Acetylcholinesterase (AchE) activity, Tumour Necrosis Factor (TNF-α), Transforming Growth Factor β (TGF-β) and 8 hydroxydeoxyguanosine (8-OHdG) levels. AlCl 3 supplementation produced significant decrease in Brain insulin Like Growth Factor (IGF-1) and Derived Neurotrophic Factor (BDNF) levels as compared to the control values. Also, AlCl 3 supplementation caused significant decline in the expression levels of nucleoporin P 62 (P 62 ) and a disintegrin and metalloproteinase 17 (ADAM 17) genes accompanied with significant elevation in the expression levels of brain cyclooxygenase (Cox-2) gene. Brain histopathological examination of AD-induced rats showed formation of amyloid plaques in hippocampus and cerebrum. Oral administration of each of selected extract (150 mg/kg b.wt) in AD-induced rats daily for 6 weeks resulted in significant decrease in brain AchE activity, TNF-α, TGF-β and 8-OHdG levels. The treatment produced significant increase in brain IGF-1 and BDNF levels as compared to AD-induced rats. The treatment with these extracts could significantly increase the gene expression levels of brain P 62 and ADAM17 accompanied with significant decrease in the expression levels of Cox-2 gene in the brain. Histopathological examination of brain tissue of the treated rats showed marked improvement in the morphological structure of the brain especially in the hippocampus and cerebrum areas. High content of terpenes, sesquiterpenes and flavonoids in the ethanolic extract of the selected plants may responsible for the anticholinesterase activity, anti-inflammatory action, antioxidant capacity and neurotrophic effect as well as antiamyloidogenic potential of these extracts. These results suggest that these extracts may effectively ameliorate the inflammation and neurodegeneration characterizing AD. Thus, these extracts may have a therapeutic application in the treatment of Alzheimer's disease.

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Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Cited by 49 publications

References 205 publications

NO-donating NSAIDs and cancer: An overview with a note on whether NO is required for their action

NO-donating NSAIDs and cancer: An overview with a note on whether NO is required for their action

Effect of Indigofera tinctoria on ?-amyloid (25-35) mediated Alzheimer’s disease in mice: Relationship to antioxidant activity

POSSIBLE THERAPEUTIC ROLE OF <I>JASONIA CANDICANS</I> AND <I>JASONIA MONTANA</I> EXTRACTS IN THE REGRESSION OF ALZHEIMERâS DISEASE IN EXPERIMENTAL MODEL

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Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Cited by 49 publications

References 205 publications

NO-donating NSAIDs and cancer: An overview with a note on whether NO is required for their action

NO-donating NSAIDs and cancer: An overview with a note on whether NO is required for their action

Effect of Indigofera tinctoria on ?-amyloid (25-35) mediated Alzheimer’s disease in mice: Relationship to antioxidant activity

POSSIBLE THERAPEUTIC ROLE OF <I>JASONIA CANDICANS</I> AND <I>JASONIA MONTANA</I> EXTRACTS IN THE REGRESSION OF ALZHEIMERâS DISEASE IN EXPERIMENTAL MODEL

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POSSIBLE THERAPEUTIC ROLE OF <I>JASONIA CANDICANS</I> AND <I>JASONIA MONTANA</I> EXTRACTS IN THE REGRESSION OF ALZHEIMERâS DISEASE IN EXPERIMENTAL MODEL