Zacharoula Konsoula1, Frank A Barile. 1. Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington DC 20057, USA.
Abstract
INTRODUCTION: Epigenetic modifications, such as histone acetylation and deacetylation, are responsible for maintaining chromatin stability. As such, they have been implicated in a wide range of neurodegenerative disorders. METHODS: Histone acetylation involves the presentation of an acetyl group to lysine residues at the N terminus of histone proteins. Conversely, histone deacetylation involves the detachment of acetyl groups. Transcriptionally active chromatin is linked to acetylated histones, and in mouse neurons, is implicated in proper learning and memory. DISCUSSION: Proper functioning of histone deacetylases (HDACs) plays a pivotal role in histone acetylation homeostasis. RESULTS: A wide range of brain disorders are associated with improper balances within histone acetylation mechanisms, resulting in transcriptional dysfunction and translational disparities. Treatment modalities with various HDAC inhibitors have emerged as potential new strategies for therapeutic intervention in neurodegenerative disease. HDAC inhibitors enhance synaptic plasticity, learning and memory in neurodegenerative disorders, such as Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). In this review, we discuss a variety of in vitro cellular models and in vivo mouse models of neurodegenerative diseases and the potential application of HDAC inhibitors to prevent and treat these disorders.
INTRODUCTION: Epigenetic modifications, such as histone acetylation and deacetylation, are responsible for maintaining chromatin stability. As such, they have been implicated in a wide range of neurodegenerative disorders. METHODS: Histone acetylation involves the presentation of an acetyl group to lysine residues at the N terminus of histone proteins. Conversely, histone deacetylation involves the detachment of acetyl groups. Transcriptionally active chromatin is linked to acetylated histones, and in mouse neurons, is implicated in proper learning and memory. DISCUSSION: Proper functioning of histone deacetylases (HDACs) plays a pivotal role in histone acetylation homeostasis. RESULTS: A wide range of brain disorders are associated with improper balances within histone acetylation mechanisms, resulting in transcriptional dysfunction and translational disparities. Treatment modalities with various HDAC inhibitors have emerged as potential new strategies for therapeutic intervention in neurodegenerative disease. HDAC inhibitors enhance synaptic plasticity, learning and memory in neurodegenerative disorders, such as Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). In this review, we discuss a variety of in vitro cellular models and in vivo mouse models of neurodegenerative diseases and the potential application of HDAC inhibitors to prevent and treat these disorders.
Authors: Louise M Collins; Luc J Adriaanse; Surabhi D Theratile; Shane V Hegarty; Aideen M Sullivan; Gerard W O'Keeffe Journal: Mol Neurobiol Date: 2014-07-29 Impact factor: 5.590