Glutamate Carboxypeptidase II Inhibition as a Novel Therapeutic Target

Autor: X M Lu, Camilo Rojas, Barbara S. Slusher, James J. Vornov, Pavel Majer, Krystyna M. Wozniak, Ajit G. Thomas, Takashi Tsukamoto
Rok vydání: 2005
Předmět:
Zdroj: Dipeptidyl Aminopeptidases in Health and Disease ISBN: 0306477173
Popis: We have shown that 2-PMPA, an inhibitor of GCP II, was neuroprotective in in vitro and in vivo models of stroke and effectively attenuated neuropathic pain in a chronic constrictive injury model. These biological effects are likely mediated by GCP II inhibition-induced decreases in extracellular glutamate and/or increases in extracellular NAAG. Therefore, GCP II inhibition may be useful in neurological disorders in which excessive glutamate transmission is pathogenic. In addition, GCP II inhibition may represent a novel glutamate regulating strategy devoid of the side effects that have hampered the development of postsynaptic glutamate receptor antagonists. A lead GCP II inhibitor is currently completing Phase I clinical testing.
Databáze: OpenAIRE