Pharmaceutical composition containing nuclear factor involved in proliferation and differentiation of central neuronal cells

Abstract

With an aim to provide a novel factor inducing proliferation of neural stem cells and differentiation of these cells into nerve cells, a pharmaceutical composition comprising 1) CRBN, 2) a nucleic acid encoding CRBN, or 3) a stem cell or a neural progenitor cell in which CRBN is expressed, a method including administering the pharmaceutical composition to a non-human animal and inducing proliferation of neural stem cells or neural progenitor cells of the non-human animal and differentiation of these cells into nerve cells, and a method for screening for a therapeutic drug for a disease of cerebral cortex or a surgical injury of cerebral cortex, using CRBN, are provided.

1 . A pharmaceutical composition comprising 1) CRBN, 2) a nucleic acid encoding CRBN, or 3) a stem cell or a neural progenitor cell in which CRBN is expressed. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the nucleic acid encoding CRBN is inserted in a virus vector. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , comprising CRBN and a protein that forms a ubiquitin ligase complex with CRBN. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , comprising the nucleic acid encoding CRBN and a nucleic acid encoding a protein that forms a ubiquitin ligase complex with CRBN. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , comprising a stem cell or a neural progenitor cell in which CRBN and a protein that forms a ubiquitin ligase complex with CRBN are expressed. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , used for treating a disease of cerebral cortex or a surgical injury of cerebral cortex. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , used for regenerating cerebral cortex. 
     
     
         8 . A method comprising administering the pharmaceutical composition according to  claim 1  to a non-human animal and proliferating a neural stem cell or a neural progenitor cell of the non-human animal. 
     
     
         9 . A method comprising administering the pharmaceutical composition according to  claim 1  to a non-human animal and differentiating a neural stem cell or a neural progenitor cell of the non-human animal into a nerve cell. 
     
     
         10 . A method for screening for a therapeutic drug for a disease of cerebral cortex or a surgical injury of cerebral cortex, comprising contacting a test substance with a ubiquitin ligase complex comprising CRBN and measuring a ubiquitin ligase activity of the ubiquitin ligase complex to select a test substance with an increased ubiquitin ligase activity. 
     
     
         11 . A method for screening for a therapeutic drug for a disease of cerebral cortex or a surgical injury of cerebral cortex, comprising culturing a neural stem cell or a neural progenitor cell in the presence of a test substance and measuring an expression level of CRBN in the neural stem cell or the neural progenitor cell to select a test substance with an increased expression level of CRBN.