Neuroprotective function of thymosin-β and its derivative peptides on the programmed cell death of chick and rat neurons

Thymosin-βs (Tβs) are small polypeptides with various biological functions, including cytoskeletal remodeling, angiogenesis, cellular migration, wound healing, and regulation of apoptosis. Recently, we found that Tβ is involved in the control of programmed cell death (PCD) of motoneurons (MNs) in chick embryo, and that the anti-apoptotic action of Tβ is independent of its actin-sequestering activity. In this study, we observed that a synthetic peptide derived from Tβ suppressed staurosporine-induced neuronal apoptosis in vitro, and PCD of chick or rat MNs in vivo. Furthermore, inhibition of Tβ4 in chick embryo by antibody significantly augmented the PCD of MNs, suggesting that secreted form of Tβ is physiological regulator of PCD. Based on these findings, we propose that extracellularly secreted Tβ is involved in the control of PCD of neurons during development, and Tβ-derived peptides could be useful for the anti-apoptotic therapy of neuropathologies related to neuronal apoptosis.