Amyloid, Cholinesterase, Melatonin, and Metals and Their Roles in Aging and Neurodegenerative Diseases

Lahiri, Debomoy K.; Chen, De Mao; Lahiri, Preeti; Bondy, Steve; Greig, Nigel H.

doi:10.1196/annals.1352.008

Cited by 35 publications

(30 citation statements)

References 82 publications

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“…All of these may be attenuated by chronic treatment with dietary melatonin [79][80][81][82][83]. Melatonin can restore the ability of the aging brain to respond to an inflammatory stimulus [19], and this is in concordance with reports of favorable effects of melatonin on the circulating immune system (described earlier).…”

Section: Specific Effects Of Melatonin On Events Relating To Brain Agingsupporting

confidence: 75%

Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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The changes associated with brain aging are discussed with emphasis on altered oxidative and inflammatory events and on mitochondrial dysfunction. Many of these changes are exacerbated in a variety of age-related neurologic diseases. This commonality has led to the idea that similar therapeutic approaches may be used in the treatment of several apparently unrelated neurodegenerative disorders. When aspects of these diseases are modeled in experimental animals and cell lines, the application of melatonin has been reported to be advantageous. The means by which melatonin can be protective probably is mediated by way of activation of melatonin receptors, of which several subtypes can be identified. This can initiate a sequence of intracellular signaling events and by activation of transcription factors lead to altered gene expression. The culmination of this cascade can lead to increased levels of antioxidant enzymes and depressed levels of inflammation. Melatonin may be useful both in the retardation of nonpathologic brain aging and in the amelioration of chronic brain disease associated with aging. The inexpensive nature and ready availability of melatonin together with its very low toxicity reinforce the need to place the beneficial properties of this agent on a firmer basis.

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Section: Specific Effects Of Melatonin On Events Relating To Brain Agingsupporting

confidence: 75%

Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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“…Cytokines like IL-1β were shown to stimulate NOS expression in various cell types [34,35]. Incubation of U-138 cells with a low dose of IL-1β in the assay did not stimulate nitrite production.…”

Section: High Dose Of Il-1β Decreased Nitrite Production In C6 Cells mentioning

confidence: 99%

“…Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) has been demonstrated to impair memory and increase NO in the temporal cortex of rats [22]. In particular, injection of the fraction Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) caused an increase of neuronal nitric oxide synthase (nNOS) and iNOS immunoreactivity in the temporal cortex and hippocampus.…”

Section: Aβ Fragment Impairs Memory and Increases No In The Temporal mentioning

confidence: 99%

“…In particular, injection of the fraction Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) caused an increase of neuronal nitric oxide synthase (nNOS) and iNOS immunoreactivity in the temporal cortex and hippocampus. In addition, there was a significant increase of reactive astrocytosis, which was accompanied by neuronal damage in the temporal cortex and hippocampus of rats injected with Aβ(25-35).…”

Section: Aβ Fragment Impairs Memory and Increases No In The Temporal mentioning

confidence: 99%

“…1 and 2). We have also characterized the effects of different neuroprotective compounds, including melatonin [35,44], to reduce and/or prevent the formation of this cascade pathway.…”

Section: Role Of Melatonin In the Inhibition Of Nox Releasementioning

confidence: 99%

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Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

Lahiri

Ghosh

Rogers

et al. 2010

Aging and Age-Related Disorders

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Role of nitric oxide in neurodegeneration and vulnerability of neuronal cells to nitric oxide metabolites and reactive oxygen species NO can also be released chemically from a group of compounds called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites is believed to be involved in several disorders, including Alzheimer's disease (AD). This chapter summarizes the role of NO and oxidative stress in neurodegeneration and describes the experimental evidence of increased vulnerability of neuronal cells to NO metabolites and other reactive oxygen species (ROS). As NO is a highly labile, unstable free gas, levels of the stable end products, such as nitrite and nitrate (NOx), were measured. When different cell types were treated with SNP, a significant level of NOx was detected in a time-and dose-dependent manner, which was more than the spontaneous release by SNP. Astrocytic, glial, and epithelial cell lines released significantly higher levels of NOx compared with neuronal cell lines after SNP treatment. Neuronal cells were more sensitive to SNP-induced cytotoxicity, as determined by lactate dehydrogenase assay. SNP-mediated toxicity is known to be due, in large part, to the accumulation of cyanide ions, and the ability of cells to protect themselves against this toxicity depends upon their levels of NO metabolites. Cell lines that generate more NOx, such as astrocytic and epithelial, are better protected against the SNP-induced toxicity than are less NOx-protecting neuronal cell lines. Our results suggest that various cell types metabolize SNP differently and that neuronal cell lines are more vulnerable than other cell types to SNP treatment. As neuronal cell lines lack an NO-generated protective mechanism, these cells are potentially primary targets for neurodegeneration by toxic agents including the free radicals and peroxynitrites.

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Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

2018

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Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration has approved drugs (e.g., rivastigmine, donepezil, galantamine, and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Looking at the wide pharmaceutical applications of heterocyclic compounds and particularly those containing benzofuran and indole ring systems, these molecular frameworks have drawn special attention from medicinal chemists for further evaluation in numerous diseases. This article focuses on the history and recent advances of benzofuran- and indole-based compounds as inhibitors of butyrylcholinesterase, acetylcholinesterase, γ-secretase, β-secretase, tau misfolding, and β-amyloid aggregation.

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Amyloid, Cholinesterase, Melatonin, and Metals and Their Roles in Aging and Neurodegenerative Diseases

Cited by 35 publications

References 82 publications

Melatonin, Oxidative Stress, and the Aging Brain

Melatonin, Oxidative Stress, and the Aging Brain

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

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