REGULATION OF HYPOXIA INDUCIBLE FACTORS VIA HISTONE DEACETYLASE 3 INHIBITOR DRUGS AND A COMPARISON BETWEEN THEIR INTERACTIONS

Abstract

Hypoxia is a condition of impaired oxygen levels in the body. This cellular response is mediated by Hypoxia-Inducible Factors (HIF), where the levels of HIF-1 are increased. This article is concerned with the cross-talk of Wnt signaling, HIF-1 α, Ubiquitin Proteasome System, and Histone Deacetylase 3 using bioinformatics softwares and databases that are an application of computer science and biology. PLMD, AutoDock, SwissDock, Swiss ADME, and Open Babel are various computational applications used under the study. It has been known that Wnt-signaling is regulated by HIF-1 in neuronal stem cells. Futhermore, high HIF-1α increases VEGF levels that lead to abnormal pathological angiogenesis, triggering the release of TGFs which leads to the accumulation of AβPP and secretion of neurotoxic peptides. This research refers to a study where valproic acid, an HDAC has been known to restore the functions of NEP and loss of the memory that had been caused by prenatal hypoxia in an adult human neuroblastoma cell line. Moreover, the other drugs,i.e. vorinostat, pracinostat, entinostat, and mocetinostat, are known to inhibit Histone deacetylase 3 activitieswere analysed using blind docking. These drugs are primarily involved in treating different types of advanced cancers like breast cancer, lymphoma, acute myelogenous leukemia, T-cell lymphoma etc. Therefore, under this study, the interaction between HIF-1α and HDAC 3 has been analyzed using PPI Network Analysis followed by molecular docking of HDAC 3 and the drugs under comparison. The results have shown Valproic acid is involved in treating neurological disorders previously but mocetinostat shows better inhibition against HDAC 3, and thus HIF-1α. Hence, these drugs under study can be used as a putative drug in the treatment of Alzheimer’s disease. The findings direct future prospects towards laboratory experiments between valproic acid, vorinostat, pracinostat, entinostat, and mocetinostat, and its inhibitory effect on HDAC 3 to prevent Alzheimer’s disease.