Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications

表观遗传学 染色质 生物 DNA甲基化 基因 遗传学 疾病 后生 表型 神经科学 机制(生物学) 计算生物学 生物信息学 基因表达 医学 病理 哲学 认识论
作者
Moshe Szyf
出处
期刊:European Neuropsychopharmacology [Elsevier BV]
卷期号:25 (5): 682-702 被引量:52
标识
DOI:10.1016/j.euroneuro.2014.01.009
摘要

Aberrant changes in gene function are believed to be involved in a wide spectrum of human disease including behavioral, cognitive and neurodegenerative pathologies. Most of the attention in last few decades have focused on changes in gene sequence as a cause of gene dysfunction leading to disease and mental health disorders. Germ line mutations or other alterations in the sequence of DNA that associate with different behavioral and neurological pathologies have been identified. However, sequence alterations explain only a small fraction of the cases. In addition there is evidence for "gene-environment" interactions in the brain suggesting mechanisms that alter gene function and the phenotype through environmental exposure. Genes are programmed by "epigenetic" mechanisms such as chromatin structure, chromatin modification and DNA methylation. These mechanisms confer on similar sequences different identities during cellular differentiation. Epigenetic differences are proposed to be involved in differentiating gene function in response to different environmental contexts and could result in alterations in functional gene networks that lead to brain disease. Epigenetic markers could serve important biomarkers in brain and behavioral diseases. Moreover, epigenetic processes are potentially reversible pointing to epigenetic therapeutics in psychotherapy.

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