Thymosin beta 4 attenuates PrP(106-126)-induced human brain endothelial cells dysfunction.

The blood-brain barrier (BBB) is a highly selective permeability barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS). The BBB is formed by cerebral endothelial cells connected by tight junctions. Prion diseases are neurodegenerative pathologies characterized by the accumulation of altered forms of the prion protein (PrP), named PrP. Thymosin beta 4 (Tβ) is an actin-sequestering peptide known to bind monomeric actin and inhibit its polymerization, and it is known to have a neuroprotective effect. However, the effect of Tβon prion disease has not yet been investigated. Therefore, in this study, we investigated the effect of Tβon prion-induced BBB dysfunction in hCMEC/D3 human cerebral endothelial cells. We found that Tβincreased the expression of tight junction protein, but reduced the ratio of F-actin to G-actin. Moreover, we showed that Tβsignificantly improved PrP (106-126)-induced vascular permeability dysfunction in hCMEC/D3 cells. Through human BBB in vitro model, we found that PrP (106-126) could disrupt tight junctions and cytoskeleton arrangement. These results suggest that Tβmay play a critical role in barrier stabilization. Furthermore, Tβmay prevent neurodegenerative diseases caused by prion-induced BBB dysfunction.