Fernández-Monreal Mónica, López-Atalaya José P, Benchenane Karim, Léveillé Frederic, Cacquevel Mathias, Plawinski Laurent, MacKenzie Eric T, Bu Guojun, Buisson Alain, Vivien Denis
University of Caen, CNRS, 14047, Caen, France.
Mol Cell Neurosci. 2004 Apr;25(4):594-601. doi: 10.1016/j.mcn.2003.11.002.
In the last few years, it has been evidenced that serine proteases play key roles in the mammalian brain, both in physiological and pathological conditions. It has been well established that among these serine proteases, the tissue-type plasminogen activator (t-PA) is critically involved in development, plasticity, and pathology of the nervous system. However, its mechanism of action remains to be further investigated. By using pharmacological and immunological approaches, we have evidenced in the present work that t-PA should be considered as a neuromodulator. Indeed, we have observed that: (i). neuronal depolarization induces a release of t-PA; (ii). this release of t-PA is sensitive to exocytosis inhibition and calcium chelation; (iii). released t-PA modulates NMDA receptor signaling and (iv). astrocytes are able to recapture extracellular t-PA through a low-density lipoprotein (LDL) receptor-related protein (LRP)-dependent mechanism.
在过去几年中，已有证据表明丝氨酸蛋白酶在哺乳动物大脑中，无论是在生理还是病理条件下都发挥着关键作用。在这些丝氨酸蛋白酶中，组织型纤溶酶原激活剂（t-PA）与神经系统的发育、可塑性和病理学密切相关，这一点已经得到充分证实。然而，其作用机制仍有待进一步研究。通过药理学和免疫学方法，我们在本研究中证明t-PA应被视为一种神经调节剂。事实上，我们观察到：（i）. 神经元去极化会诱导t-PA的释放；（ii）. t-PA的这种释放对外排抑制和钙螯合敏感；（iii）. 释放的t-PA调节NMDA受体信号传导，并且（iv）. 星形胶质细胞能够通过低密度脂蛋白（LDL）受体相关蛋白（LRP）依赖性机制重新摄取细胞外t-PA。
