The Epigenome as a therapeutic target for Parkinson’s disease
Shane V. Hegarty
Aideen M. Sullivan
Gerard W. O’Keeffe
摘要：Parkinson’s disease (PD) is a common, progressive neurodegenerative disease characterised by degener-ation of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. hTis ar-ticle ifrst discusses the present evidence implicating global, and dopaminergic neuron-speciifc, alterations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes that mediate this process are at-tractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neu-roprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.
机标关键词：therapeutic potentialdopaminergic neuronshistone acetylationhistone acetyltransferasehistone deacetylasefuture researchsmall molecule
资助基金：Studies in the authors’ laboratories are supported by grants from the Irish Research Council(R15897)Studies in the authors’ laboratories are supported by grants from the Irish Research Council( SVH/AS/G’OK)the Na-tional University of Ireland(R16189)the Na-tional University of Ireland( SVH/AS/G’OK)
论文发表日期：2016-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：4( 1735-1738 )
英文信息