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阿尔茨海默病:表观遗传学关联及相关危险因素。

Alzheimer's Disorder: Epigenetic Connection and Associated Risk Factors.

机构信息

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

Govt. College of Pharmacy, Rohru, District Shimla, Himachal Pradesh-171207, India.

出版信息

Curr Neuropharmacol. 2020;18(8):740-753. doi: 10.2174/1570159X18666200128125641.

Abstract

The gene based therapeutics and drug targets have shown incredible and appreciable advances in alleviating human sufferings and complexities. Epigenetics simply means above genetics or which controls the organism beyond genetics. At present it is very clear that all characteristics of an individual are not determined by DNA alone, rather the environment, stress, life style and nutrition play a vital part in determining the response of an organism. Thus, nature (genetic makeup) and nurture (exposure) play equally important roles in the responses observed, both at the cellular and organism levels. Epigenetics influence plethora of complications at cellular and molecular levels that includes cancer, metabolic and cardiovascular complications including neurological (psychosis) and neurodegenerative disorders (Alzheimer's disease, Parkinson disease etc.). The epigenetic mechanisms include DNA methylation, histone modification and non coding RNA which have substantial impact on progression and pathways linked to Alzheimer's disease. The epigenetic mechanism gets deregulated in Alzheimer's disease and is characterized by DNA hyper methylation, deacetylation of histones and general repressed chromatin state which alter gene expression at the transcription level by upregulation, downregulation or silencing of genes. Thus, the processes or modulators of these epigenetic processes have shown vast potential as a therapeutic target in Alzheimer's disease.

摘要

基于基因的治疗方法和药物靶点在减轻人类痛苦和复杂性方面取得了令人难以置信和显著的进展。表观遗传学是指超越遗传学或控制超越遗传学的生物体的机制。目前很明显,个体的所有特征并非仅由 DNA 决定,而是环境、压力、生活方式和营养在决定生物体的反应方面起着至关重要的作用。因此,在细胞和机体水平上,个体的先天因素(遗传构成)和后天因素(暴露)同样重要。表观遗传学影响细胞和分子水平上的多种并发症,包括癌症、代谢和心血管并发症,包括神经(精神病)和神经退行性疾病(阿尔茨海默病、帕金森病等)。表观遗传机制包括 DNA 甲基化、组蛋白修饰和非编码 RNA,它们对与阿尔茨海默病相关的进展和途径有重大影响。在阿尔茨海默病中,表观遗传机制会失调,表现为 DNA 过度甲基化、组蛋白去乙酰化和普遍抑制的染色质状态,这些状态会通过上调、下调或沉默基因来改变转录水平的基因表达。因此,这些表观遗传过程的过程或调节剂已显示出在阿尔茨海默病治疗中具有巨大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a84b/7536832/f6f082969e79/CN-18-740_F1.jpg

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