GSK3β 5'-flanking DNA Methylation and Expression in Alzheimer’s Disease Patients

Nicolia, Vincenzina; Ciraci, Viviana; Cavallaro, Rosaria A.; Ferrer, Isidre; Scarpa, Sigfrido; Fuso, Andrea

doi:10.2174/1567205014666170203153325

Cited by 23 publications

(25 citation statements)

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“…Among the kinases identified to be responsible for tau hyperphosphorylation, GSK-3β plays an important role in the pathological changes of tau protein in AD [ 23 ]. Data collected in humans show increased activation of GSK-3β in early-stage AD [ 24 ], while a consistent inhibition was observed in late-stage AD [ 25 , 26 ], thus suggesting that GSK-3β-mediated tau phosphorylation is among the earliest events during the progression of the pathology. Increasing evidence shows that tau in dendrites plays a key role in Aβ-induced detrimental effects.…”

Section: Introductionmentioning

confidence: 93%

The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy

Bukke

Moola

Villani

et al. 2020

IJMS

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Alzheimer’s disease (AD) is an age-related dementia and neurodegenerative disorder, characterized by Aβ and tau protein deposition impairing learning, memory and suppressing synaptic plasticity of neurons. Increasing evidence suggests that there is a link between the glucose and glutamate alterations with age that down-regulates glucose utilization reducing glutamate levels in AD patients. Deviations in brain energy metabolism reinforce the development of AD by hampering glutamate levels in the brain. Glutamate is a nonessential amino acid and the major excitatory neurotransmitter synthesized from glucose. Alterations in cerebral glucose and glutamate levels precede the deposition of Aβ plaques. In the brain, over 40% of neuronal synapses are glutamatergic and disturbances in glutamatergic function have been implicated in pathophysiology of AD. Nevertheless, targeting the glutamatergic system seems to be a promising strategy to develop novel, improved therapeutics for AD. Here, we review data supporting the involvement of the glutamatergic system in AD pathophysiology as well as the efficacy of glutamatergic agents in this neurodegenerative disorder. We also discuss exciting new prospects for the development of improved therapeutics for this devastating disorder.

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Section: Introductionmentioning

confidence: 93%

The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy

Bukke

Moola

Villani

et al. 2020

IJMS

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“…129 A further study identified hypomethylation of GSK3B in an in vitro experiment mimicking AD-related pathology and postmortem AD samples. 130 Intriguingly, only patients in the initial disease stage exhibited GSK3β upregulation. 130 A memory-enhancing gene, reelin (RELN), has also been highly implicated in AD.…”

Section: Neurochemical Processesmentioning

confidence: 99%

“…130 Intriguingly, only patients in the initial disease stage exhibited GSK3β upregulation. 130 A memory-enhancing gene, reelin (RELN), has also been highly implicated in AD. It was shown to bind apolipoprotein E receptor 2 (ApoER2) or verylow-density liporeceptor to facilitate the migration of neurons and synaptic transmission.…”

Section: Neurochemical Processesmentioning

confidence: 99%

DNA methylation in the pathology of Alzheimer's disease: from gene to cognition

Poon

Tse

Lim

2020

Annals of the New York Academy of Sciences

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Alzheimer's disease (AD) is a debilitating disorder that manifests with amyloid beta plaque deposition, neurofibrillary tangles, neuronal loss, and severe cognitive impairment. Although much effort has been made to decipher the pathogenesis of this disease, the mechanisms causing these detrimental outcomes remain obscure. Over the past few decades, neuroepigenetics has emerged as an important field that, among other things, explores how reversible modifications can change gene expression to control behavior and cognitive abilities. Among epigenetic modifications, DNA methylation requires further elucidation for the conflicting observations from AD research and its pivotal role in learning and memory. In this review, we focus on the essential components of DNA methylation, the effects of aberrant methylation on gene expressions in the amyloidogenic pathway and neurochemical processes, as well as memory epigenetics in Alzheimer's disease.

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“…Recently Martínez-Iglesias et al [354] analyzed the content of 5mC and 5hmC, and the expression of DNMT3a-responsible for de novo methylation [354] showing that global 5mC and 5hmC levels are significantly lower in AD mouse model as compared to healthy animals. Conversely, other studies reported no significant differences between healthy and AD brain samples [354], or even an increase of methylation and hydroxymethylation levels in different regions of the AD brain [354].…”

Section: Impact Of Dietary Factors On Dna Methylationmentioning

confidence: 99%

Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

Atlante

Amadoro

Bobba

et al. 2020

Cells

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A new epoch is emerging with intense research on nutraceuticals, i.e., “food or food product that provides medical or health benefits including the prevention and treatment of diseases”, such as Alzheimer’s disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota–gut–brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.

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GSK3β 5'-flanking DNA Methylation and Expression in Alzheimer’s Disease Patients

Abstract: These results point out that GSK3β hyperactivity, and then NFTs formation, could come into function at an early stage of the disease and then turn off at the last stages.

Cited by 23 publications

References 0 publications

The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy

The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy

DNA methylation in the pathology of Alzheimer's disease: from gene to cognition

Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

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