Microenvironment of HMGB1 “Clusters”: A Potential Drug Target for Cancer and Diabetes

Abstract

The quest for potential therapeutic strategies to treat inflammatory diseases represents one of the topical progresses in the field of medical sciences. Statistical data has shown that in the eastern world developing countries such as Indonesia, diseases such as Diabetes Mellitus, Alzheimer’s, and cancer are amongst the main causes of death. High Mobility Group Box 1 (HMGB1) is a late mediator of those pathophysiological diseases, which makes it a potential target for drug development. Despite its intracellular role in controlling gene expression and managing architectural assembly of DNA, the HMGB1 which is released by damaged cells has found to interact with cell-surface receptors such as Receptor for Advanced Glycation End-products (RAGE) and Toll-like Receptor (TLR), subsequently activating a signal cascade which then triggers various diseases. The self-association of HMGB1 is proven to be crucial for its DNA-related biological functions. We found that this self-association is influenced by several factors, such as ionic strength, pH, divalent metal cations especially zinc, and redox environment. The self-association of HMGB1 possibly influences its interaction with the receptors and the concomitant inflammatory responses. Further investigation on the detailed mechanism of self-association of HMGB1 in regards to the ligand-receptor interaction is still ongoing.



Author Information
Wresti Listu Anggayasti, Independent Researcher, Indonesia
Ricardo Mancera, Curtin University of Technology, Australia
Steven Bottomley, Curtin University of Technology, Australia
Erik Helmerhorst, Curtin University of Technology, Australia

Paper Information
Conference: IICSEEHawaii2017
Stream: Environmental Sustainability & Human Consumption: Human and Life Sciences

This paper is part of the IICSEEHawaii2017 Conference Proceedings (View)
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