Prothymosin Alpha: An Alarmin and More

Current Medicinal Chemistry
Pinelopi SamaraWolfgang Voelter

Abstract

Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similarly to molecules termed as "alarmins". Our research team pioneered the elucidation of the mechanisms underlying the observed activities of proTα. We were the first to demonstrate that proTα levels increase during normal and abnormal cell proliferation. We showed that proTα acts pleiotropically, inducing immunomodulatory effects on immune cell populations. We revealed that the immunoreactive region of proTα is the carboxyterminal decapeptide proTα(100-109) and both molecules stimulate innate immune responses, signaling through Toll-like receptors (TLRs), specifically TLR-4. We reported that proTα and proTα(100-109) bind on the surface of human neutrophils on sites involving TLR-4, and cell activation is complemented by cytoplasmic calcium ion influx. Further, we showed that proTα and proTα(100-109) act as adjuvants upstream of lymphocyte stimulation and, in the presence of antigen, promote the expansion of antigen-reactive...Continue Reading

Citations

Nov 28, 2017·Zygote : the Biology of Gametes and Early Embryos·Massimo Venditti, Sergio Minucci
Aug 8, 2019·Current Medicinal Chemistry·Chrysoula-Evangelia KarachaliouEvangelia Livaniou
Feb 12, 2021·Frontiers in Cell and Developmental Biology·Cristiana PistonoTarja Malm

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