TY - JOUR
T1 - Is tissue-type plasminogen activator a neuromodulator?
AU - Fernández-Monreal, Mónica
AU - López-Atalaya, José P.
AU - Benchenane, Karim
AU - Léveillé, Frederic
AU - Cacquevel, Mathias
AU - Plawinski, Laurent
AU - MacKenzie, Eric T.
AU - Bu, Guojun
AU - Buisson, Alain
AU - Vivien, Denis
N1 - Funding Information:
This work was supported by grants from the Medical Research Foundation (M. Fernández-Monreal), the French Ministry of Research and Technology (K. Benchenane), the Regional Council of Lower Normandy (J.P. López-Atalaya, M. Cacquevel), the University of Caen and FEDER.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mcn.2003.11.002
DO - 10.1016/j.mcn.2003.11.002
M3 - Article
C2 - 15080889
AN - SCOPUS:11144353905
SN - 1044-7431
VL - 25
SP - 594
EP - 601
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 4
ER -