Long-term oral melatonin alleviates memory deficits, reduces amyloid-β deposition associated with downregulation of BACE1 and mitophagy in APP/PS1 transgenic mice

Sun, Cuimei; Qiu, Xueliang; Wang, Ying; Liu, Jianqiang; Li, Qiang; Jiang, Hong; Li, Shuai; Song, ChaoYuan

doi:10.1016/j.neulet.2020.135192

Cited by 34 publications

(20 citation statements)

References 20 publications

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“…This might reflect increased activity of the fundamental clock protein Bmal1, one of whose transcriptional targets is Nrf2 [55][56][57]. MLT administration has been found to benefit cognitive function, lessen tau phosphorylation, and decrease amyloid β levels in multiple models of AD in mice, albeit it is unclear to what extent antioxidant effects mediate these benefits [58][59][60][61][62]. Remarkably, PCB also has been reported to boost expression of Nrf2 and its transcriptional target heme oxygenase-1 (HO-1) [63,64].…”

Section: Phase Two Induction and Support For Glutathione Synthesismentioning

confidence: 99%

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

McCarty

DiNicolantonio

Lerner

2021

IJMS

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Oxidative stress and increased cytoplasmic calcium are key mediators of the detrimental effects on neuronal function and survival in Alzheimer’s disease (AD). Pathways whereby these perturbations arise, and then prevent dendritic spine formation, promote tau hyperphosphorylation, further amplify amyloid β generation, and induce neuronal apoptosis, are described. A comprehensive program of nutraceutical supplementation, comprised of the NADPH oxidase inhibitor phycocyanobilin, phase two inducers, the mitochondrial antioxidant astaxanthin, and the glutathione precursor N-acetylcysteine, may have important potential for antagonizing the toxic effects of amyloid β on neurons and thereby aiding prevention of AD. Moreover, nutraceutical antioxidant strategies may oppose the adverse impact of amyloid β oligomers on astrocyte clearance of glutamate, and on the ability of brain capillaries to export amyloid β monomers/oligomers from the brain. Antioxidants, docosahexaenoic acid (DHA), and vitamin D, have potential for suppressing microglial production of interleukin-1β, which potentiates the neurotoxicity of amyloid β. Epidemiology suggests that a health-promoting lifestyle, incorporating a prudent diet, regular vigorous exercise, and other feasible measures, can cut the high risk for AD among the elderly by up to 60%. Conceivably, complementing such lifestyle measures with long-term adherence to the sort of nutraceutical regimen outlined here may drive down risk for AD even further.

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Section: Phase Two Induction and Support For Glutathione Synthesismentioning

confidence: 99%

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

McCarty

DiNicolantonio

Lerner

2021

IJMS

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“…Effects of melatonin on mitophagy have been described but are complicated and depend on the cell type and study conditions. Some studies have reported that melatonin promotes mitophagy [ 131 , 132 , 133 , 134 ], but others show inhibition [ 135 , 136 ]. If the data are carefully analyzed, it appears that mitophagy promotion is the predominant aspect of melatonin.…”

Section: Mitochondria and Melatoninmentioning

confidence: 99%

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Tan¹,

Hardeland

2020

Molecules

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Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen’s spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host’s tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

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“…Blood samples of the melatonin group demonstrated significant reduction of inflammatory factors, NF-κB, TNF-α, IL-6 and S100β and an On account of melatonin's plethora of neuroprotective features, stroke-induced dementia stands as a significant therapeutic target for melatonin-based treatment. In APP/PSI mice, a model of AD, long-term administration of melatonin ameliorated spatial learning and memory loss, curtailing Aβ accumulation and mitochondrial dysfunction [73]. Oxidative injury in the brain is a major factor inducing cognitive impairment and memory loss in AD.…”

Section: Novel Evidence Supporting Melatonin As An Effective Therapeutic Agent In Strokementioning

confidence: 99%

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

et al. 2020

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Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke by mitigating neuroinflammation and accelerating brain tissue restoration. Melatonin treatment includes injection of exogenous melatonin, pineal gland grafting and melatonin-mediated stem cell therapy. This review will discuss the current preclinical and clinical studies investigating melatonin-based therapeutics to treat stroke.

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Long-term oral melatonin alleviates memory deficits, reduces amyloid-β deposition associated with downregulation of BACE1 and mitophagy in APP/PS1 transgenic mice

Cited by 34 publications

References 20 publications

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

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