Antioxioxidant and antiapoptotic effects of Thymosin 4 in A-induced SH-SY5Y cells via the 5-HTR1A/ERK axis

Alzheimer's disease (AD) is a common amnestic cognitive impairment characterised by beta-amyloid (A beta) plaques deposit in the brain of the elderly. AD is a yet incurable disease due to its unknown exact pathogenesis and unavailability of effective remedies in clinical application. Thymosin beta 4 (T beta 4) is a housekeeping protein that plays important role in cell proliferation, migration and differentiation. It has the ability to protect and repair neurons however it is still unclear involvement in AD. Therefore, the aim of this study is to elucidate the role and mechanism of T beta 4 in mediating the improvement of AD. AD-like cell model was constructed in neuroblastoma cell line SH-SY5Y treated with A beta. Overexpression of T beta 4 were done using lentivirus infection and downregulation through siRNA transfection. We performed western blot and flow cytometry to study the apoptosis and standard kits to measure the oxidative stress-associated biomarkers. There is significant increased in viability and decreased apoptosis in T beta 4 overexpression group compared to control. Furthermore, overexpression of T beta 4 suppressed the expression of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax meanwhile upregulated the expression of anti-apoptotic gene Bcl-2. T beta 4 alleviated oxidative damage by reducing MDA, LDH and ROS and increasing SOD and GSH-PX in A beta-treated SH-SY5Y cells. We found that T beta 4 inhibit ERK/p38 MAPK pathway and intensify the expression of 5-HTR1A. Additionally, we showed that upregulation of 5-HTR1A dampened the T beta 4 to activate ERK signalling. In conclusion, our study revealed the neuroprotective role of T beta 4 in AD which may open up new therapeutic applications in AD treatment.