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Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Sakyo, Kyoto 606-8502, Japan
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8501, Japan
* Author to whom correspondence should be addressed.
Received: 21 August 2012; in revised form: 20 November 2012 / Accepted: 18 December 2012 / Published: 27 December 2012
Abstract: Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of epigenetic memory is also a major concern in the clinical translation of the Nobel Prize-winning discovery of induced pluripotent stem cell technology. Consequently, there is an increasing interest in the development of novel epigenetic switch-based therapeutic strategies that could potentially restore the heritable changes in epigenetically inherited disorders. Here we give a comprehensive overview of epigenetic inheritance and suggest the prospects of therapeutic gene modulation using epigenetic-based drugs, in particular histone deacetylase inhibitors. This review suggests that there is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels. The development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach for restoring defects in an altered epigenome and may offer a sustainable solution to some unresolved clinical issues.
Keywords: epigenetic inheritance; chemical mimics; HDAC inhibitors; regenerative medicine; cancer treatment; programmable genetic switches; histone code; epigenetic switch based therapy; future medicine
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Pandian, G.N.; Sugiyama, H. Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature. Pharmaceuticals 2013, 6, 1-24.
Pandian GN, Sugiyama H. Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature. Pharmaceuticals. 2013; 6(1):1-24.
Pandian, Ganesh N.; Sugiyama, Hiroshi. 2013. "Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature." Pharmaceuticals 6, no. 1: 1-24.