HMGB1 in nervous system diseases: A common biomarker and potential therapeutic target

Abstract

High-mobility group box-1 (HMGB1) is a nuclear protein associated with early inflammatory changes upon extracellular secretion expressed in various cells, including neurons and microglia. With the progress of research, neuroinflammation is believed to be involved in the pathogenesis of neurological diseases such as Parkinson's, epilepsy, and autism. As a key promoter of neuroinflammation, HMGB1 is thought to be involved in the pathogenesis of Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, and amyotrophic lateral sclerosis. However, in the clinic, HMGB1 has not been described as a biomarker for the above-mentioned diseases. However, the current preclinical research results show that HMGB1 antagonists have positive significance in the treatment of Parkinson's disease, stroke, traumatic brain injury, epilepsy, and other diseases. This review discusses the possible mechanisms by which HMGB1 mediates Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, amyotrophic lateral sclerosis, and the potential of HMGB1 as a biomarker for these diseases. Future research needs to further explore the underlying molecular mechanisms and clinical translation.

Keywords: HMGB1; biomarker; nervous system diseases; neuroinflammation; therapeutic target.

Figure 1

Schematic view of HMGB1 structure.

Figure 2

HMGB1 can be actively secreted by immune cells or passively secreted by necrotic or damaged cells. HMGB1 binds to RAGE and TLR4 to activate downstream signaling pathways, resulting in the upregulation of cytokines by pro-inflammatory cells. As HMGB1 antagonists, GL and EP can inhibit the release of HMGB1. The anti-HMGB1 mAb neutralizes HMGB1.