ABSTRACT
AIMS: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder seriously endangering the physical and mental health of the elderly, while no effective treatments and drugs in clinical practice are available. Thymosin ß4 (Tß4) is a multifunctional polypeptide involved in many physiological and pathological processes including AD. This study aims to understand the function and molecular mechanism of Tß4 in the development of AD. MAIN METHODS: Neuroblastoma cell line SH-SY5Y was treated with ß-amyloid (Aß) to induce AD-like pathological changes, which serves as Alzheimer's disease model. Tß4 was overexpressed in SH-SY5Y cells by lentivirus infection, and downregulated by siRNA transfection. Apoptosis of transfected SH-SY5Y cells after Aß-treatment was examined by western blot and flow cytometry. Apoptotic proteins and Tß4-related signaling pathways were also investigated by western blot. KEY FINDINGS: We found that Tß4 overexpression increased viability and suppressed apoptosis of Aß-treated SH-SY5Y cells. Tß4 ameliorated oxidative damage and suppressed reactive oxygen species production in Aß-treated SH-SY5Y cells. Consistently, Tß4 overexpression down-regulated the expression levels of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax, while up-regulated the expression level of anti-apoptotic gene Bcl-2 in Aß-stimulated SH-SY5Y cells. Mechanistically, we demonstrated that Tß4 dampened ERK/p38 MAPK signaling and enhanced 5-HTR1A expression in Aß-treated SH-SY5Y cells. Moreover, we revealed that Tß4 inhibited the activation of ERK pathway through up-regulating 5-HTR1A in Aß-treated SH-SY5Y cells. SIGNIFICANCE: Taken together, our findings provide evidences to support the neuroprotective role of Tß4 and might open up new therapeutic applications of Tß4 in AD treatment.
