Screening of binary neuroprotective DAMPs activity

胸腺素原a(ProtA)是一种核蛋白，在细胞核、胞浆和细胞外环境中发挥着多功能的自我保护作用。我们已经发现，Prota是通过非囊泡方式从缺血应激的神经元中释放出来的，并通过抗坏死机制发挥着独特的神经保护作用。此外，细胞外Prota还通过神经免疫系统发挥抗细胞凋亡的作用。关于应激诱导的释放方式，Prota被归类为新的神经保护性损伤相关分子模式(DAMP)。ProTA的细胞外抗缺血损伤作用是通过两种不同的质膜受体介导的。在本研究中，我们揭示了Prota通过这些受体发挥神经保护作用的机制。此外，我们成功地将ProTa的功能结构域确定为受体上的多肽水平，这是治疗脑梗塞的候选药物靶点。

Prothymosin a (ProTa), a nuclear protein plays multi-functional roles in the nucleus, cytosol, and extracellular environment in terms of auto-protection. We have already revealed that ProTa is released from neurons on ischemic stress through non-vesicular manner and exerts a unique form of neuroprotection through an anti-necrotic mechanism. In addition, extracellular ProTa also exerts an anti-apoptosis through neuroimmunological system. Regarding manner of stress-induced release, ProTa is categorized as novel neuroprotective damage-associated molecular patterns (DAMPs). The extracellular role of ProTa against ischemia-induced damages is mediated through different two plasma membrane receptors. In the present study, we revealed mechanism of ProTa for the neuroprotection via these receptors. Furthermore, we successfully identified functional domains of ProTa as a peptide level on receptor, a candidate druggable target in the treatment of brain infarct.