Anti-high mobility group box protein 1 monoclonal antibody downregulating P-glycoprotein as novel epilepsy therapeutics

Abstract

Epilepsy, a neurological illness, is characterized by recurrent uncontrolled seizures. There are many treatments of options that can be used as the therapy of epilepsy. However, anti-seizure medications as the primary treatment choice for epilepsy show many possible adverse effects and even pharmacoresistance to the therapy. High Mobility Group Box 1 (HMGB1) as an initiator and amplifier of the neuroinflammation is responsible for the onset and progression of epilepsy by overexpressing P-glycoprotein on the blood brain barrier. HMGB1 proteins then activate TLR4 in neurons and astrocytes, in which proinflammatory cytokines are produced. Anti-HMGB1 mAb works by blocking the HMGB1, reducing inflammatory activity in the brain that may affect epileptogenesis. Through the process, anti-HMGB1 mAb reduces the TLR4 activity and other receptors that may involve in promote signal of epilepsy such as RAGE. Several studies have shown that anti-HMGB1 has the potential to inhibit the increase in serum HMGB1 in plasma and brain tissue. Further research is needed to identify the mechanism of the inhibiting of overexpression of P-glycoprotein through anti-HMGB1 mAb.

Neuroinflammation: A Common Pathway in Alzheimer’s Disease and Epilepsy

“…have shown favorable results in controlling neuroinflammation, and subsequently the progression of AD [18]. Meanwhile, inhibitors of TLR3 or TLR4 expressed by microglia [19] and anti-high motility group box-1 (HMGB-1) [59] in preclinical studies have also demonstrated a significant reduction in epileptic seizures by disrupting the inflammatory mechanisms. Inflammation-targeting small molecules in the management of AD and seizures were seen to produce positive neurologic outcomes due to their smaller size and low molecular weight that could penetrate the CNS domain [18,19].…”