Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders.docVIP

Pharmaceuticals 2012, 5, 369-383; doi:10.3390/ph5040369 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders Takeo Kubota *, Hirasawa Takae and Kunio Miyake Department of Epigenetic Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 490-3898, Japan; E-Mails: takae@yamanashi.ac.jp (H.T.); kmiyake@yamanashi.ac.jp (K.M.) * Author to whom correspondence should be addressed; takeot@yamanashi.ac.jp; Tel.: +81-55-273-9557; Fax: +81-55-273-9561. Received: 29 February 2012; in revised form: 23 March 2012 / Accepted: 27 March 2012 / Published: 5 April 2012 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.