Method for examining central nervous system diseases and method for screening therapeutic agents

Abstract

The present invention relates to a method for screening and identifying therapeutic agents or preventive agents for central nervous system diseases which comprises assaying a suppressing effect of a test substance on an expression of a splicing variant transcribed from presenilin-2 gene and to a method for examining central nervous system diseases which comprises detecting an expression of a splicing variant transcribed from presenilin-2 gene in a test sample originated from an animal individual.

1 . A method for screening and identifying a therapeutic agent or preventive agent for central nervous system disease which comprises assaying a suppressing effect of a test substance on an expression of a splicing variant transcribed from presenilin-2 gene.  
     
     
         2 . The method according to  claim 1 , wherein expression of a splicing variant is the expression of a splicing variant in nerve cell.  
     
     
         3 . The method according to  claim 2 , wherein expression of a splicing variant is induced by exposure of nerve cell to oxidative stress.  
     
     
         4 . The method according to  claim 1 , wherein expression of a splicing variant is the expression of a splicing variant in animal brain tissue.  
     
     
         5 . The method according to  claim 1 , wherein said splicing variant is a splicing variant lacking exon 5 of presenilin-2 gene.  
     
     
         6 . The method according to  claim 5 , wherein said splicing variant is a splicing variant lacking exon 5 and exon 8 of presenilin-2 gene.  
     
     
         7 . The method according to  claim 1 , wherein said splicing variant is a splicing variant lacking exon 3 of presenilin-2 gene.  
     
     
         8 . The method according to  claim 1 , wherein said splicing variant is a splicing variant lacking exon 3 and exon 4 of presenilin-2 gene and having a portion of an intron sequence.  
     
     
         9 . The method according to any one of  claims 1  to  6 , wherein said central nervous system disease is Alzheimer's disease.  
     
     
         10 . A therapeutic agent or preventive agent for Alzheimer's disease having an effect of suppressing an expression of a splicing variant transcribed from presenilin-2 gene and lacking exon 5.  
     
     
         11 . A therapeutic agent or preventive agent for central nervous system disease screened or identified by any one of the methods according to  claims 1  to  8 .  
     
     
         12 . A therapeutic agent or preventive agent for Alzheimer's disease screened or identified by any one of the methods according to  claims 1  to  8 .  
     
     
         13 . A method for detecting a splicing variant lacking exon 5 of presenilin-2 gene comprising detecting nucleic acid containing at least the 705th and 706th bases in the base sequence described in SEQ ID NO: 2.  
     
     
         14 . A method for detecting a splicing variant lacking exon 3 of presenilin-2 gene comprising detecting nucleic acid containing at least the 329th and 330th bases in the base sequence described in SEQ ID NO: 3.  
     
     
         15 . A method for detecting a splicing variant lacking exon 3 and exon 4 of presenilin-2 gene and having a portion of an intron comprising detecting nucleic acid containing at least the 330th to 409th bases in the base sequence described in SEQ ID NO: 4.  
     
     
         16 . A nucleic acid having a base sequence which is identical or complementary to a splicing variant lacking exon 5 of presenilin-2 gene.  
     
     
         17 . The nucleic acid according to  claim 16  having a base sequence selected from (1) the base sequence described in SEQ ID NO: 2, (2) the base sequence lacking the 995th to 1093rd bases in SEQ ID NO: 2, and (3) a base sequence complementary to said (1) or (2).  
     
     
         18 . A recombinant plasmid containing the nucleic acid according to  claim 15 .  
     
     
         19 . A polypeptide originated from a splicing variant lacking exon 5 of presenilin-2 gene, said polypeptide either (1) having an amino acid sequence described in the bottom of SEQ ID NO: 5, or (2) having an amino acid sequence in which one or a plurality of the amino acid residues are added, deleted or substituted in an amino acid sequence described in SEQ ID NO: 5.  
     
     
         20 . A DNA coding for the polypeptide according to  claim 19 .  
     
     
         21 . A DNA according to  claim 20  having the base sequence described in the top of SEQ ID NO: 5.  
     
     
         22 . A recombinant plasmid containing the DNA according to  claim 20.