Institut National De La Sante Et De La Recherche Medicale

Commissariat &#xc0; L'&#xc9;nergie Atomique Et Aux &#xc9;nergies Alternatives

Les Laboratoires Servier

Christophe Bosc

Annie Andrieux

Philippe Delagrange

Didier Job

Eric Denarier

Muriel Vernet

Leticia Peris

Chrystelle Aillaud

Marie-José Moutin

Marie-Jose Moutin

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 &#x3b1;-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 Vasohibin or Vasohibin/SVBP complex.

Methods and pharmaceutical compositions for treating tubulin carboxypeptidases associated diseases

The invention concerns transgenic or recombinant non-human mammals, wherein the expression of the gene coding for a microtubule associated protein (MAP) is modified (STOP gene) (inactivation or overexpression) and their uses in screening medicines useful in schizophrenia and schizo-affective disorders, with anxious, paranoiac or depressive component.

Transgenic or recombinant non-human mammals and their uses in screening psychoactive medicines

Growing community of inventors

Grenoble, France

Christophe Bosc