公开(公告)号：US20060277611A1

公开(公告)日：2006-12-07

申请号：US10557109

申请日：2004-05-13

申请人： Wendy Mia Balemans ,  Diederik Willem Moechars ,  Thomas Steckler ,  Kim Cryns

发明人： Wendy Mia Balemans ,  Diederik Willem Moechars ,  Thomas Steckler ,  Kim Cryns

IPC分类号： A01K67/027 ,  C12Q1/68 ,  G01N33/567

CPC分类号： A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0356 ,  C12N9/16 ,  G01N33/573

摘要： This invention relates to the functional characterization of myo-inositol monophosphatase 2 (IMPA2), one of the enzymes acting in the phosphatidyl inositol signaling pathway. In particular, the present invention provides evidence that IMPA2 is associated with depression- and anxiety inducing conditions, in particular anxiety and affective disorders. In a first aspect the present invention provides the use of an IMPA2 enzyme in an assay to identify anti-anxiety or an anti-depression compounds. In particular to the use of an isolated polynucleotide encoding said IMPA2 protein, wherein said IMPA2 protein is preferably being selected from polynucleotides encoding the mouse, rat or human IMPA2 enzyme. It is thus an object of the present invention to provide a method for identifying anti-anxiety or anti-depression compounds wherein said compounds are capable of enhancing neuronal plasticity, said method comprising the steps of: a) providing a composition comprising an IMPA2 protein; b) contacting the IMPA2 protein with the test compound; and c) measuring the activity of the IMPA2 protein wherein a decrease in the IMPA2 activity in the presence of the test compound is an indicator of an anti-anxiety or anti-depression compound. In these assays the activity of the IMPA2 protein is assessed by measuring the hydrolysis of myo-inositol 1-phosphate to generate inositol and inorganic phosphate, in particular by measuring the accumulation of either myo-inositol monophosphate product in the form of radiolabeled inositol or inorganic phosphate (Pi) in the form of radiolabeled 32Pi or in a colorimetric assay. The compositions comprising the IMPA2 protein could either be cellular extracts, whole cells or organisms expressing the IMPA2 proteins according to the invention.

摘要翻译： 本发明涉及作用于磷脂酰肌醇信号通路的酶之一的肌醇单磷酸酶2（IMPA2）的功能表征。 特别地，本发明提供证据表明IMPA2与抑郁和焦虑诱发病症特别是焦虑和情感障碍有关。 在第一方面，本发明提供了IMPA2酶在测定中用于鉴定抗焦虑或抗抑郁化合物的用途。 具体涉及使用编码所述IMPA2蛋白质的分离的多核苷酸，其中所述IMPA2蛋白质优选选自编码小鼠，大鼠或人IMPA2酶的多核苷酸。 因此，本发明的目的是提供一种用于鉴定抗焦虑或抗抑郁化合物的方法，其中所述化合物能够增强神经元的可塑性，所述方法包括以下步骤：a）提供包含IMPA2蛋白质的组合物; b）使IMPA2蛋白质与测试化合物接触; 和c）测量IMPA2蛋白的活性，其中在测试化合物存在下IMPA2活性的降低是抗焦虑或抗抑郁化合物的指标。 在这些测定中，通过测量肌醇-1-磷酸肌酸水解产生肌醇和无机磷酸酯来评估IMPA2蛋白的活性，特别是通过测量放射性标记的肌醇或无机形式的肌醇单磷酸酯产物的积累 磷酸盐（Pi）以放射性标记的32 PIP的形式或在比色测定中。 包含IMPA2蛋白质的组合物可以是表达本发明的IMPA2蛋白质的细胞提取物，全细胞或生物体。