Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells

Takahashi, Muneaki; Chin, Yo; Nonaka, Takashi; Hasegawa, Masato; Watanabe, Nobuo; Arai, Takao

doi:10.1016/j.neulet.2011.12.067

Cited by 10 publications

(2 citation statements)

References 30 publications

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“…Furthermore, beta amyloid production is increased upon nitrotyrosination of presenilin-1 in aging rat hippocampal neurons, which parallels the situation observed with PSEN1 mutations associated with familial AD . In addition, prolonged NO exposure can induce the formation of cytoplasmic tau oligomers in SH-SY5Y cells, corroborating the potential mechanism underlying tau neuropathogenesis in AD …”

Section: Gut Microbiome Microglia Amyloids Nitric Oxide and Alzheimer...supporting

confidence: 69%

Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders

Tse

2017

ACS Chem. Neurosci.

144

122

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Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g., superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation. NO also instigates a down-regulated secretion of brain-derived neurotrophic factor, which is essential for neuronal survival, development and differentiation, synaptogenesis, and learning and memory. The gut-brain axis denotes communication between the enteric nervous system (ENS) of the GI tract and the central nervous system (CNS) of the brain, and the modes of communication include the vagus nerve, passive diffusion and carrier by oxyhemoglobin. Amyloid precursor protein that forms amyloid beta plaques in AD is normally expressed in the ENS by gut bacteria, but when amyloid beta accumulates, it compromises CNS functions. Escherichia coli and Salmonella enterica are among the many bacterial strains that express and secrete amyloid proteins and contribute to AD pathogenesis. Gut microbiota is essential for regulating microglia maturation and activation, and activated microglia secrete significant amounts of iNOS. Pharmacological interventions and lifestyle modifications to rectify aberrant NO signaling in AD include NOS inhibitors, NMDA receptor antagonists, potassium channel modulators, probiotics, diet, and exercise.

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Section: Gut Microbiome Microglia Amyloids Nitric Oxide and Alzheimer...supporting

confidence: 69%

Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders

Tse

2017

ACS Chem. Neurosci.

144

122

View full text Add to dashboard Cite

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“…This finding points to a specific mechanism for how nitrosative stress could potentially induce one of the hallmarks of AD [ 37 ]. Furthermore, although the presence of S-nitrosylated proteins and tau has been demonstrated in AD, prolonged NO exposure can induce the formation of cytoplasmic tau oligomers in SH-SY5Y cells, providing evidence of a potential mechanism underlying tau neuropathogenesis in AD [ 53 ]. Experiments in cell lines using overexpression of AD markers have provided clues to mechanism but this research has a limited capacity to model AD effectively.…”

Section: The Contribution Of Nitrosative Stress To a βmentioning

confidence: 99%

Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

Balez

Ooi

2015

Oxidative Medicine and Cellular Longevity

115

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Alzheimer's disease (AD) is a neurodegenerative disorder involving the loss of neurons in the brain which leads to progressive memory loss and behavioral changes. To date, there are only limited medications for AD and no known cure. Nitric oxide (NO) has long been considered part of the neurotoxic insult caused by neuroinflammation in the Alzheimer's brain. However, focusing on early developments, prior to the appearance of cognitive symptoms, is changing that perception. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability. A potential mechanism for augmentation of excitability by NO is via modulation of voltage-gated potassium channel activity (Kv7 and Kv2). Identification of the ionic mechanisms and signaling pathways that mediate this protection is an important next step for the field. Harnessing the protective role of NO and related signaling pathways could provide a therapeutic avenue that prevents synapse loss early in disease.

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First-in-class DAPK1/CSF1R dual inhibitors: Discovery of 3,5-dimethoxy-N-(4-(4-methoxyphenoxy)-2-((6-morpholinopyridin-3-yl)amino)pyrimidin-5-yl)benzamide as a potential anti-tauopathies agent

Farag

Hassan

Jeong

et al. 2019

European Journal of Medicinal Chemistry

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Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells

Cited by 10 publications

References 30 publications

Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders

Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders

Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

First-in-class DAPK1/CSF1R dual inhibitors: Discovery of 3,5-dimethoxy-N-(4-(4-methoxyphenoxy)-2-((6-morpholinopyridin-3-yl)amino)pyrimidin-5-yl)benzamide as a potential anti-tauopathies agent

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