Τίτλος:
Histone lysine methyltransferase SETDB1 as a novel target for central nervous system diseases
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Epigenetic changes that regulate chromatin structure have a major impact in genome stabilization and maintenance of cellular homeostasis, been recently implicated in the pathophysiology of central nervous system (CNS). Aberrant expression and dysregulation of histone modification enzymes has been associated with the development of several CNS disorders, revealing these enzymes as putative targets for drug development and novel therapeutic approaches. SETDB1 is a histone lysine methyltransferase responsible for the di- and tri-methylation of histone 3 (H3) at lysine (K) 9 in euchromatic regions further promoting gene silencing through heterochromatin formation. By this way, SETDB1 has been shown to regulate gene expression and influence normal cellular homeostasis required for nervous system function while it is also implicated in the pathogenesis of CNS disorders. Among them, brain tumors, schizophrenia, Huntington's disease, autism spectrum disorders along with alcohol-induced fetal neurobehavioral deficits and Prader-Willi syndrome are representative examples, indicating the aberrant expression and function of SETDB1 as a common pathogenic factor. In this review, we focus on SETDB1-associated molecular mechanisms implicated in CNS physiology and disease while we further discuss current pharmacological approaches targeting SETDB1 enzymatic activity with beneficial effects. © 2020 Elsevier Ltd
Συγγραφείς:
Markouli, M.
Strepkos, D.
Chlamydas, S.
Piperi, C.
Περιοδικό:
Progress In Neurobiology
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
histone H3; histone lysine methyltransferase; histone; histone lysine methyltransferase; lysine; SETDB1 protein, human, autism; brain tumor; cognitive defect; epigenetics; fetus; histone modification; human; Huntington chorea; mental disease; nerve cell differentiation; neurologic disease; pathogenesis; Prader Willi syndrome; priority journal; protein expression; protein targeting; Review; schizophrenia; substance abuse; central nervous system disease; metabolism; methylation, Central Nervous System Diseases; Histone-Lysine N-Methyltransferase; Histones; Humans; Lysine; Methylation
DOI:
10.1016/j.pneurobio.2020.101968
