Thymosin Beta 4 Protects Hippocampal Neuronal Cells against PrP (106-126) via Neurotrophic Factor Signaling

Prion protein peptide (PrP) has demonstrated neurotoxicity in brain cells, resulting in the progression of prion diseases with spongiform degenerative, amyloidogenic, and aggregative properties. Thymosin beta 4 (Tβ₄) plays a role in the nervous system and may be related to motility, axonal enlargement, differentiation, neurite outgrowth, and proliferation. However, no studies about the effects of Tβ₄ on prion disease have been performed yet. In the present study, we investigated the protective effect of Tβ₄ against synthetic PrP (106-126) and considered possible mechanisms. Hippocampal neuronal HT22 cells were treated with Tβ₄ and PrP (106-126) for 24 h. Tβ₄ significantly reversed cell viability and reactive oxidative species (ROS) affected by PrP (106-126). Apoptotic proteins induced by PrP (106-126) were reduced by Tβ₄. Interestingly, a balance of neurotrophic factors (nerve growth factor and brain-derived neurotrophic factor) and receptors (nerve growth factor receptor p75, tropomyosin related kinase A and B) were competitively maintained by Tβ₄ through receptors reacting to PrP (106-126). Our results demonstrate that Tβ₄ protects neuronal cells against PrP (106-126) neurotoxicity via the interaction of neurotrophic factors/receptors.