Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

Abstract

The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

“…Furthermore, DNA methylation contributes to natural human variation [ 4 ]. Epigenetic modifications are reversible and can potentially be targeted by pharmacological and dietary interventions [ 6 ]. A series of epigenetic drugs have been developed ( Table 1 ), and some of these compounds have been approved by the Food and Drug Administration (FDA) for the treatment of neoplastic processes [ 7 , 8 , 9 ].…”

Personalizing health care: feasibility and future implications

“…Whether this happens remains to be seen, especially given that, despite many decades of scientific advances, only a few genotyping or phenotyping tests are currently being used routinely in clinical practice [4,5,10,11,13,16,21,36],[105,121,122]. This is because of increasing knowledge and awareness that a given patient’s genomic and phenotypic make-up is appreciably more complex than initially believed, as well as the influence of environmental factors [1,9-12,16,36,49,117,122]. As a result, different approaches are required to separate diseases into different subgroups.…”

Epigenetics of Brain Disorders: The Paradigm of Alzheimer ’s Disease

“…Epigenomic modifications are involved in a great variety of physiological and pathological conditions; of major importance are those related with major problems of health such as cardiovascular disorders, obesity, cancer, inflammatory processes, and brain disorders [11,12]. A good paradigm on the influence of epigenetic factors on human pathology is the oncogenic process in some types of cancer.…”

“…Over 95% of the eukaryotic genome is transcribed into non-coding RNAs and less than 5% is translated. LncRNA-mediated epigenetic regulation depends on lcnRNA interactions with proteins or genomic DNA via RNA secondary structures [10].Epigenomic modifications are involved in a great variety of physiological and pathological conditions; of major importance are those related with major problems of health such as cardiovascular disorders, obesity, cancer, inflammatory processes, and brain disorders [11,12]. A good paradigm on the influence of epigenetic factors on human pathology is the oncogenic process in some types of cancer.…”