Analysis of HMGB1 Signaling Pathway in Ischemic Stroke

High mobility group protein 1 (HMGB1) is a ubiquitous nuclear protein that plays an essential role in cell death, immunity and inflammation, thrombosis, and remodeling and repair. HMGB1 can be released passively from necrotic neurons or actively secreted by microglia, macrophages/monocytes, and neutrophils. As an endogenous danger-associated molecular pattern (DAMP) protein that mediates brain inflammation and brain injury, HMGB1 also plays an important role in the mechanism of cerebral ischemic injury. Numerous studies have shown that ischemic brain injury in adults results in the translocation of HMGB1 from the neuronal nucleus to the brain parenchyma. However, the role of HMGB1 in cerebral ischemia is complex and still unclear. HMGB1 has attracted attention as a novel key molecular target in cerebral ischemic injury.

Fig. 1. Potential mechanisms by which HMGB1 contributes to stroke pathogenesis. (Ye et al., 2019)

Our Services

Through our state-of-the-art facilities and advanced technologies, Ace Therapeutics helps clients to unravel the possible mechanisms of HMGB1 signaling pathway in ischemic stroke and develop HMGB1 as a biomarker for stroke diagnosis and prognosis.

Identification and Validation of HMGB1-related Targets in Stroke

We provide high-throughput sequencing and bioinformatics analysis of multiple receptors and transduction pathways of HMGB1 to find relevant targets for stroke.

• Receptor for advanced glycation end products (RAGE)
• Toll-like receptor (TLR)-2 and TLR-4
• TLR downstream signaling regulators: p38, MyD88, TGF-β activated kinase 1 (TAK1) and TAK1 binding protein 2 (TAB2)
• NF-κB
• Pro-inflammatory factors: TNF-α, iNOS, ICAM-1, IL-1β, IL-6, IL-8 and COX-2

Analysis of the Role of HMGB1 in Experimental Models of Stroke

We provide in vitro and animal models of ischemic stroke to investigate the involvement of HMGB1 in the pathogenesis of ischemic stroke and reperfusion injury, and the effects of different redox-modified HMGB1 on ischemic stroke.

• Regulation of HMGB1 in inflammation
• Excitotoxic injury caused by HMGB1 release
• BBB damage caused by HMGB1 release
• Regulation of autophagy by HMGB1
• Relationship between HMGB1 and mitochondrial oxidative stress
• Relationship between HMGB1 and the immune system

Stroke Drugs Development Services Targeting HMGB1

Based on the different roles of HMGB1 in the early and late stages of ischemic stroke, our experts are committed to developing different strategies to inhibit the expression, release, and activity of HMGB1 to ameliorate brain damage, including blocking the release of HMGB1 from the cells, binding to and neutralizing the activity of HMGB1, blocking the activation of HMGB1 or its interactions with specific receptors, and inhibiting the HMGB1-initiated downstream signaling initiated by HMGB1. We help clients develop stroke drugs that target HMGB1.

• Small-molecule inhibitors of HMGB1
• Anti-HMGB1 antibodies
• HMGB1 A Box
• RNA interference (RNAi): HMGB1 siRNA, HMGB1 shRNA

Ace Therapeutics provides reliable services to investigate the mechanism of HMGB1 in ischemic stroke. We work closely with clients to provide customized solutions to meet the unique requirements of each research project. If you are interested in our services, please do not hesitate to contact us!

1. Ye, Y., et al. (2019). The role of high mobility group box 1 in ischemic stroke. Frontiers in Cellular Neuroscience, 13, 127.