Epigenetic Landscape of Parkinson's Disease: Emerging Role in Disease Mechanisms and Therapeutic Modalities

Abstract

Parkinson's disease (PD) is a complex multifactorial disorder marked by extensive system-wide pathology, including a substantial loss of nigrostriatal dopaminergic neurons. The etiology of PD remains elusive, but there is considerable evidence that, in addition to well-defined genetic mechanisms environmental factors play a crucial role in disease pathogenesis. How the environment might influence the genetic factors and contribute to disease development and progression remains unclear. In recent years, epigenetic mechanisms such as DNA methylation, chromatin remodeling and alterations in gene expression via non-coding RNAs have begun to be revealed as potential factors in PD pathogenesis. Epigenetic modulation exists throughout life, beginning in prenatal stages, is dependent on the lifestyle, environmental exposure and genetic makeup of an individual and may serve as a missing link between PD risk factors and development of the disease. This chapter sheds light on the emerging role of epigenetics in disease pathogenesis and on prospective interventional strategies for the therapeutic modulation of PD. © 2013 The American Society for Experimental NeuroTherapeutics, Inc.