A BRD's (BiRD's) eye view of BET and BRPF bromodomains in neurological diseases

摘要

Neurological disorders (NLDs)6 are among the top leading causes for disability worldwide. Dramatic changes in the epigenetic topography of the brain and nervous system have been found in many NLDs. Histone lysine acetylation has prevailed as one of the well characterised epigenetic modifications in these diseases. Two instrumental components of the acetylation machinery are the evolutionarily conserved Bromodomain and PHD finger containing (BRPF) and Bromo and Extra terminal domain (BET) family of proteins, also referred to as acetylation 'readers'. Several reasons, including their distinct mechanisms of modulation of gene expression and their property of being highly tractable small molecule targets, have increased their translational relevance. Thus, compounds which demonstrated promising results in targeting these proteins have advanced to clinical trials. They have been established as key role players in pathologies of cancer, cardiac diseases, renal diseases and rheumatic diseases. In addition, studies implicating the role of these bromodomains in NLDs are gaining pace. In this review, we highlight the findings of these studies, and reason for the plausible roles of all BET and BRPF members in NLDs. A comprehensive understanding of their multifaceted functions would be radical in the development of therapeutic interventions.