TAT-W61 peptide reduces the inflammation and apoptosis by inhibiting the binding S100b to the V-domain of Rage during ischemic stroke

Abstract Ischemic stroke is a nervous system disease associated with high mortality and morbidity rates. Currently, there are no neuroprotective drugs for this disease. S100 calcium-binding protein b (S100b), which is abnormally expressed in the cerebrospinal fluid of patients, can bind to various other proteins and exacerbate the progression of stroke; receptor for advanced glycation end-products (Rage) is one of these proteins. To inhibit the occurrence of this interaction, a peptide (TAT-W61) based on the V-domain of S100b that interacts with Rage was produced. This study aimed to use TAT-W61 to reduce the levels of inflammation and apoptosis after ischemic stroke and to improve learning memory and motor dysfunction. In this study, S100b and Rage expression increased after ischemic stroke. Possible binding sites of S100b on Rage were mapped through molecular docking and polar–contact assays. In immunoprecipitation experiments, TAT-W61 inhibited the binding of S100b to Rage after ischemic stroke. TAT-W61 peptide, derived from Rage, could reduce the inflammatory and apoptotic response caused by ischemic stroke. It may also improve the infarct volume of the pathological injury and reduce the apoptotic rate. In particular, the TAT-W61 peptide could significantly improve learning, memory, and motor dysfunction in an ischemic stroke model. TAT-W61 peptide may help alleviate ischemic stroke injury.