UNIVERSITE GRENOBLE ALPES;LES LABORATOIRES SERVIER;COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIE ALTERNATIVES;INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)
发明人:
ANDRIEUX, ANNIE,MOUTIN, MARIE-JOSE,BOSC, CHRISTOPHE,AILLAUD, CHRYSTELLE,PERIS, LETICIA,DELAGRANGE, PHILIPPE
申请号：
CA3079865
公开号：
CA3079865A1
申请日:
2018.10.26
申请国别(地区):
CA
年份:
2019
代理人:
摘要：
Using chemical proteomics with a potent unique irreversible inhibitor, inventors found that major brain tubulin carboxypeptidase (TCP)is a complex of vasohibin-1 (VASH1) with the Small Vasohibin-Binding Protein (SVBP). VASH1 and its homologue vasohibin-2 (VASH2), when complexed with SVBP, exhibit robust and specific Tyr/Phe carboxypeptidase activity on microtubules. Accordingly inventors are the first to identify the enzymatic activity of vasohibin and vasohibin/SVBP complex. Knock down of vasohibins or SVBP in cultured neurons results in a marked reduction of tyrosinated a-tubulin levels and onset of severe differentiation defects. Furthermore, knock down of vasohibins disrupts neuronal migration in developing mouse neocortex. These results establish vasohibin/SVBP complexes as TCP enzymes. Accordingly, the present invention relates methods and pharmaceutical compositions for treating tubulin carboxypeptidases (TCP) associated diseases such as neurological disorders and cardiovascular diseases with an inhibitor of activity or expression of Vasohibinor Vasohibin/SVBP complex.
