Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Eur J Pharmacol. 2019 Sep 5;858:172487. doi: 10.1016/j.ejphar.2019.172487. Epub 2019 Jun 20.
High mobility group box 1 (HMGB1) is a ubiquitous protein, released passively by necrotic tissues or secreted actively by stressed cells. Extracellular HMGB1 is a typical damage-associated molecular pattern (DAMP) molecule which generates different redox types through binding with several receptors and signalling molecules, aggravating a range of cellular responses, including inflammation. HMGB1 is reported to participate in the pathogenesis of inflammatory diseases, through the interaction with pivotal transmembrane receptors, including the receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4). This review aims to highlight the role of HMGB1 in the innate inflammatory response describing its interaction with several cofactors and receptors that coordinate its downstream effects. Novel and underexplored HMGB1 binding molecules that have been actively involved in HMGB1-mediated inflammatory diseases/conditions with therapeutic potential are further discussed.
高迁移率族蛋白 B1（HMGB1）是一种普遍存在的蛋白质，可通过坏死组织被动释放或应激细胞主动分泌。细胞外 HMGB1 是一种典型的损伤相关分子模式（DAMP）分子，通过与几种受体和信号分子结合，产生不同的氧化还原类型，加剧一系列细胞反应，包括炎症。据报道，HMGB1 通过与关键的跨膜受体（包括晚期糖基化终产物受体（RAGE）和 Toll 样受体 4（TLR-4））相互作用，参与炎症性疾病的发病机制。本综述旨在强调 HMGB1 在先天炎症反应中的作用，描述其与几种协同因子和受体的相互作用，这些协同因子和受体协调其下游效应。进一步讨论了新型和研究不足的 HMGB1 结合分子，这些分子在 HMGB1 介导的炎症性疾病/病症中具有治疗潜力。
