Epigenetic mechanisms in Alzheimer&amp;#39;s disease

Balázs, R.

doi:10.2147/dnnd.s37341

Cited by 7 publications

(10 citation statements)

References 174 publications

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“…Recently, it has been observed that environmental factors even transient ones in early life can induce AD-like pathogenesis in association with aging (Wu et al, 2008a ). Furthermore, a difference in DNA methylation patterns typical of brain region and aging has been identified in this context (Balazs, 2014 ). In this regard, a recent study by Hernandez et al examined the DNA methylation patterns in >27,000 CpG sites from donors ranging in age 4 months to 102 years and a strong relationship was found between DNA methylation and aging.…”

Section: Alzheimer’s Disease and Epigeneticsmentioning

confidence: 99%

“…The acetylation of histones is a modification associated generally to transcriptional activity that indicates access of the transcription machinery to the genes and thus active mechanisms (Strahl and Allis, 2000 ; Balazs, 2014 ). This effect could be explained by the chemistry of this modification in which an acetyl group (−COCH3) is incorporated to an amino terminal residue and thus, the positive charge of histones is reduced, inducing a minor interaction with DNA resulting in a decrease of the chromatin compaction (Figures 2A,B ; Shahbazian and Grunstein, 2007 ).…”

Section: Histone Acetylationmentioning

confidence: 99%

“…Until now, most of the studies have analyzed DNA methylation in the brain of AD patients (Balazs, 2014 ). In this regard, a variety of studies suggest a genome-wide decrease in DNA methylation present in aging and AD patients (Table 2 ; Mastroeni et al, 2011 ).…”

Section: Alzheimer’s Disease and Epigeneticsmentioning

confidence: 99%

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Epigenetic mechanisms in neurological and neurodegenerative diseases

Landgrave-Gómez

Mercado-Gómez

Guevara‐Guzmán

2015

Front. Cell. Neurosci.

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The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS) and its regulation in diseases is one of the most interesting processes of contemporary neuroscience. In the last decade, a growing body of literature suggests that long-term changes in gene transcription associated with CNS’s regulation and neurological disorders are mediated via modulation of chromatin structure. “Epigenetics”, introduced for the first time by Waddington in the early 1940s, has been traditionally referred to a variety of mechanisms that allow heritable changes in gene expression even in the absence of DNA mutation. However, new definitions acknowledge that many of these mechanisms used to perpetuate epigenetic traits in dividing cells are used by neurons to control a variety of functions dependent on gene expression. Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS. Moreover, environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A (acetyl-coA), nicotinamide adenine dinucleotide (NAD + ) and beta hydroxybutyrate (β-HB), regulates some of these epigenetic modifications, linking in a precise way environment with gene expression. This manuscript will portray what is currently understood about the role of epigenetic mechanisms in the function and homeostasis of the CNS and their participation in a variety of neurological disorders. We will discuss how the machinery that controls these modifications plays an important role in processes involved in neurological disorders such as neurogenesis and cell growth. Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases. Finally, we will highlight possible future directions in the field of epigenetics and neurological disorders.

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Section: Alzheimer’s Disease and Epigeneticsmentioning

confidence: 99%

Section: Histone Acetylationmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic mechanisms in neurological and neurodegenerative diseases

Landgrave-Gómez

Mercado-Gómez

Guevara‐Guzmán

2015

Front. Cell. Neurosci.

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“…There is a fair chance that factors in addition to aging, eg, hypertension, diabetes, obesity, and inflammatory disorders, may have an effect on AD and be inducing epigenetic changes as well or might induce AD-like pathogenesis at a young age. Associations between DNA-methylation patterns in the brain and aging are possible44 and have been reported in various regions of the brain 45. Since DNA epigenetic mechanisms have a role in memory formation and its maintenance, just as decrease in DNA methylation deteriorates neuronal plasticity, leading to memory loss, it is speculated that understanding of epigenetic mechanisms is important to understand aging and associated complexities in AD patients 46.…”

Section: Epigenetics and Admentioning

confidence: 99%

<p>Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics</p>

Tiwari¹,

Atluri²,

Kaushik³

et al. 2019

IJN

843

525

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Currently, 47 million people live with dementia globally, and it is estimated to increase more than threefold (~131 million) by 2050. Alzheimer’s disease (AD) is one of the major causative factors to induce progressive dementia. AD is a neurodegenerative disease, and its pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles made of hyperphosphorylated τ-protein in cortical and limbic areas of the human brain. It is characterized by memory loss and progressive neurocognitive dysfunction. The anomalous processing of APP by β-secretases and γ-secretases leads to production of Aβ 40 and Aβ 42 monomers, which further oligomerize and aggregate into senile plaques. The disease also intensifies through infectious agents like HIV. Additionally, during disease pathogenesis, the presence of high concentrations of Aβ peptides in central nervous system initiates microglial infiltration. Upon coming into vicinity of Aβ, microglia get activated, endocytose Aβ, and contribute toward their clearance via TREM2 surface receptors, simultaneously triggering innate immunoresponse against the aggregation. In addition to a detailed report on causative factors leading to AD, the present review also discusses the current state of the art in AD therapeutics and diagnostics, including labeling and imaging techniques employed as contrast agents for better visualization and sensing of the plaques. The review also points to an urgent need for nanotechnology as an efficient therapeutic strategy to increase the bioavailability of drugs in the central nervous system.

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“…Histone methylation and demethylation, mediated by histone methylases (HMTs) and demethylases (HDMTs), respectively, also contribute to neurodegenerative progression. Those enzymes have a high specificity as they usually modify one single lysine per histone which may be translated into activation or repression of transcription [ 19 , 55 , 101 , 102 , 124 , 125 ]. Histone methylations H3K4, H3K36, and H3K79 are associated with the activation of gene expression, whereas methylations at H3K9, H3K27, and H4K20, correspond to gene silencing.…”

Section: Main Epigenetic Hallmarks Of Neurodegenerationmentioning

confidence: 99%

Pharmacoepigenomic Interventions as Novel Potential Treatments for Alzheimer’s and Parkinson’s Diseases

Teijido

Cacabelos

2018

IJMS

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Cerebrovascular and neurodegenerative disorders affect one billion people around the world and result from a combination of genomic, epigenomic, metabolic, and environmental factors. Diagnosis at late stages of disease progression, limited knowledge of gene biomarkers and molecular mechanisms of the pathology, and conventional compounds based on symptomatic rather than mechanistic features, determine the lack of success of current treatments, including current FDA-approved conventional drugs. The epigenetic approach opens new avenues for the detection of early presymptomatic pathological events that would allow the implementation of novel strategies in order to stop or delay the pathological process. The reversibility and potential restoring of epigenetic aberrations along with their potential use as targets for pharmacological and dietary interventions sited the use of epidrugs as potential novel candidates for successful treatments of multifactorial disorders involving neurodegeneration. This manuscript includes a description of the most relevant epigenetic mechanisms involved in the most prevalent neurodegenerative disorders worldwide, as well as the main potential epigenetic-based compounds under investigation for treatment of those disorders and their limitations.

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Epigenetic mechanisms in Alzheimer's disease

Cited by 7 publications

References 174 publications

Epigenetic mechanisms in neurological and neurodegenerative diseases

Epigenetic mechanisms in neurological and neurodegenerative diseases

<p>Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics</p>

Pharmacoepigenomic Interventions as Novel Potential Treatments for Alzheimer’s and Parkinson’s Diseases

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