Histone Deacetylase Inhibitors: An Innovative Revolution as Epigenetic Modifiers

This review article explores the target based epigenetic mechanisms as well as existing and potential therapeutic role of HDACIs in various malignant and non-malignant diseases. Epigenetic modifications to histone proteins, such as acetylation and deacetylation, play a critical role in gene transcription and expression. Acetylation, which is catalysed by histone acetyl transferases enzymes, activates gene expression by converting chromatin into a less compact, transcriptionally active state. Histone deacetylase enzymes catalyse chromatin deacetylation, which condenses it into a closed structure. As a result, transcriptional factors cannot access DNA and gene expression is suppressed. The activity of HATs and HDACS must be balanced for normal gene expression. Increased HDAC activity can result in an imbalance in protein acetylation, resulting in hypoacetylation, tight chromatin structure, and gene suppression. This erroneous gene suppression is a hallmark of a number of cancers and other diseases, including neurodegenerative disorders. Histone Deacetylase Inhibitors have the potential to restore histone acetylation balance, thereby reversing the silencing of pathological genes. As a result, HDACIs act as epigenetic modifiers by modifying gene expression without affecting DNA sequence. Preclinical studies with valproic acid and other HDACIs have extended their potential value in diseases other than neoplasms such as neurodegenerative diseases, psychiatric diseases, autoimmune disorders, inflammatory diseases, diabetes mellitus, cardiovascular diseases and AIDS. Vorinostat, Belinostat Panobinostat and Romidepsin are FDA approved HDACIs. Valproic acid, and many others are in different phases of clinical trials. Data sources were articles published in medical journals and bibliographic database Medline.