Epigenetics in Alzheimer’s Disease

Gao, Xiaodie; Chen, Qiang; Yang, Hua; Tan, Jie; Liu, Zheng; Zhou, Yan; Zou, Zhenyou

doi:10.3389/fnagi.2022.911635

Cited by 37 publications

(40 citation statements)

References 185 publications

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“…Given that epigenetic and mitoepigenetic changes can be detected even in the periphery, they have the potential to be included in the list of AD risk factors and biomarkers and to become therapeutic targets for new drugs. The epigenetics of AD, including epigenetic modulation by microRNAs, and possible treatment opportunities have been described and discussed in detail in a number of reviews [ 83 , 84 , 85 , 86 , 87 , 88 , 89 ].…”

Section: Risk Factors and Biomarkers Of Alzheimer’s Diseasementioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.

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Section: Risk Factors and Biomarkers Of Alzheimer’s Diseasementioning

confidence: 99%

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar

2022

Biomolecules

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“…DNA methylation controls the expression of genes related to Alzheimer's disease under the action of related enzymes. Changes in related enzymes result in a decrease in histone methylation, which results in the inactivation of memory-related genes and abnormal p53 levels [ 28 ]. Through its interactions with cellular factors, viral factors, and RNAs that can promote the development of various disorders, p53 plays a vital role in the progression of neurodegenerative diseases.…”

Section: Reviewmentioning

confidence: 99%

“…As a result, inhibiting p53 may be an appropriate target for restoring neural functioning [ 29 ]. Inhibitors of histone acetyltransferases (HATs) and histone deacetylases (HDACs) can restore these alterations and prevent Alzheimer's disease [ 28 ]. Increased phosphorylation of histones is linked to the clinical phenomenon of Alzheimer's disease, resulting in memory impairment.…”

Section: Reviewmentioning

confidence: 99%

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Alzheimer’s Disease: Understanding Its Novel Drug Delivery Systems and Treatments

Dhingra¹,

Choudhari²

2022

Cureus

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Around the world, there are no fewer than 24 million people who suffer from dementia. Through 2040, this number is expected to rise steadily every 20 years. Alzheimer's disease (AD), the most prevalent kind of dementia, is characterised by a steady deterioration in cognitive function that most often begins with memory loss. Alzheimer's disease (AD) is considered to be one of the leading causes of morbidity in the elderly. Around 5 million people in the United States have Alzheimer's disease. Still, because AD is common in the older and greying population, its prevalence is expected to rise dramatically in the coming decades. As the disease progresses, people with Alzheimer's disease frequently become dependent on caregivers. The Alzheimer's-diseased brain is characterised neuropathologically by diffuse and neuritic extracellular amyloid plaques, which are often ringed by dystrophic neurites and intracellular neurofibrillary tangles. This particular disease is characterised by the presence of reactive microgliosis and the destruction of neurons, white matter, and synapses. The present review is done to study and learn about new treatments and novel drug delivery systems that may provide benefits to patients with AD. With the new drugs, treatments, constant care requirements, and lost productivity, Alzheimer's has a substantial financial impact on society. Therefore, better management and therapy are crucial. In this overview, we will briefly go through the current knowledge base about AD, covering the functions of beta-amyloid, tau proteins, and stem cell therapy, and elaborating on novel diagnostic and therapeutic interventions.

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“…Epigenetics, which involves noncoding-RNAs, histone modifications, and DNA methylation, is the study of potentially heritable changes in gene expression without changes in the DNA sequences or genotype. [4][5][6] Histone methylation, a process in that methyl group is transferred to amino acids of histone proteins, has been associated with cancer, cardiovascular disease, and Alzheimer's disease [7][8][9]. Histone methyltransferases and histone demethylases, which methylate and demethylate protein lysine and arginine residues, have crucial roles in the control of histone methylation regulation [10,11].…”

Section: Introductionmentioning

confidence: 99%

Antitumor Effect of Demethylzeylasteral (T-96) on Triple-Negative Breast Cancer via LSD1-Mediate Epigenetic Mechanisms

Shen

Jiang

et al. 2022

Analytical Cellular Pathology

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Background and Purpose. Breast cancer ranks first in the incidence of female tumors. Triple-negative breast cancer (TNBC), one type of breast cancer, is more aggressive and has a worse prognosis. Demethylzeylasteral (T-96) is isolated from Tripterygium wilfordii Hook F. Our previous study found that T96 could inhibit TNBC invasion via suppressing the canonical and noncanonical TGF-β signaling pathways. However, the antitumor effects and mechanisms of T-96 on TNBC have not been studied. This study is aimed at investigating the antitumor effect and mechanism of T-96 on breast cancer. Experimental approach. MTT assay, Live and Dead cell assay, and TUNEL were used to observe the antitumor effect of breast cancer cells treated with T-96. siRNA of LSD1, Co-IP, and molecular docking were used to explore the direct target and mechanism of T-96. Subcutaneous murine xenograft models were used to detect the efficacy of T-96 antitumor activity in vivo. Key Results. T-96 was more susceptible to inducing the apoptosis of highly metastatic TNBC cell lines (SUM-1315). An abnormal level of histone methylation is a crucial characteristic of metastatic cancer cells. LSD1 is a histone demethylase. We found that T-96 could significantly decrease the protein expression of LSD1, increase its target protein PTEN expression and enhance histone methylation. T-96 could also down-regulate the PI3K/AKT signaling pathway, which could be blocked by PTEN. Knockdown of LSD1 by siRNA blocked the pharmacological activity of T-96. And the molecular docking predicted T-96 processed affinity toward LSD1 through hydrogen bonding. Finally, T-96 was evaluated in a murine xenograft model of SUM-1315 cells. And T-96 could significantly inhibit tumor growth without showing marked toxicity. Conclusions & Implications. The results illustrated that T-96 exerted antitumor activity in highly metastatic TNBC by inactivating the LSD1 function.

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Epigenetics in Alzheimer’s Disease

Cited by 37 publications

References 185 publications

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Alzheimer’s Disease: Understanding Its Novel Drug Delivery Systems and Treatments

Antitumor Effect of Demethylzeylasteral (T-96) on Triple-Negative Breast Cancer via LSD1-Mediate Epigenetic Mechanisms

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