Methods and compositions for treating neurodegenerative disorders and alzheimer's disease and improving normal memory

Abstract

The disclosure relates generally to neurodegenerative disorders and more specifically to a group of presenilin/G-protein/c-src binding polypeptides and methods of use for modulating signaling and progression of Alzheimer's disease.

1 - 59 . (canceled) 
     
     
         60 . A method of inhibiting the production of Aβ in a subject comprising contacting a cell in the subject with an isolated polypeptide consisting essentially of an amino acid sequence from the N-terminal fragment of PS-1 (SEQ ID NO:2), wherein the fragment is selected from the group consisting of:
 (i) 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRSLGHPEPLSNGRP 
                 
             
                
                
               
            
           
         
         (ii) SEQ ID NO:6 further including 1-10 additional amino acids at the N- and/or C-terminal end(s), 
         (iii) a polypeptide that is 85% identical to SEQ ID NO:6 having 1-5 conservative amino acid substitutions, 
         (iv) a sequence consisting essentially of (iii) further including 1-10 additional amino acids at the N- and/or C-terminal end(s), wherein the polypeptide inhibits cell-cell interaction, inhibits Aβ production or binds to a β-APP, and 
         (v) combinations of any of the foregoing, wherein the isolated polypeptide inhibits production of Aβ in a cell in the subject. 
       
     
     
         61 . The method of  claim 60 , wherein the subject is a human. 
     
     
         62 . The method of  claim 61 , wherein the subject has Alzheimer's disease. 
     
     
         63 . The method of  claim 60 , wherein the isolated polypeptide consists essentially of RRSLGHPEPLSNGRP (SEQ ID NO:6) or SEQ ID NO:6 further including 1-10 additional amino acids at the N- and/or C-terminal end(s). 
     
     
         64 . The method of  claim 62 , wherein the isolated polypeptide consists essentially of RRSLGHPEPLSNGRP (SEQ ID NO:6) or SEQ ID NO:6 further including 1-10 additional amino acids at the N- and/or C-terminal end(s). 
     
     
         65 . The method of  claim 64 , wherein the isolated polypeptide consists of 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRSLGHPEPLSNGRP. 
                 
             
                
                
               
            
           
         
       
     
     
         66 . A method of inhibiting the production of Aβ in a cell comprising contacting a mammalian cell with an isolated polypeptide consisting essentially of an amino acid sequence from the N-terminal fragment of PS-1 (SEQ ID NO:2), wherein the fragment is selected from the group consisting of:
 (i) 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRSLGHPEPLSNGRP 
                 
             
                
                
               
            
           
         
         (ii) SEQ ID NO:6 further including 1-10 additional amino acids at the N- and/or C-terminal end(s), 
         (iii) a polypeptide that is 85% identical to SEQ ID NO:6 having 1-5 conservative amino acid substitutions, 
         (iv) a sequence consisting essentially of (iii) further including 1-10 additional amino acids at the N- and/or C-terminal end(s), wherein the polypeptide inhibits cell-cell interaction, inhibits Aβ production or binds to a β-APP, and 
         (v) combinations of any of the foregoing, wherein the isolated polypeptide inhibits production of Aβ in the cell. 
       
     
     
         67 . The method of  claim 66 , wherein the mammalian cell is a human cell. 
     
     
         68 . The method of  claim 66 , wherein the isolated polypeptide consists essentially of RRSLGHPEPLSNGRP (SEQ ID NO:6) or SEQ ID NO:6 further including 1-10 additional amino acids at the N- and/or C-terminal end(s). 
     
     
         69 . The method of  claim 67 , wherein the isolated polypeptide consists essentially of RRSLGHPEPLSNGRP (SEQ ID NO:6) or SEQ ID NO:6 further including 1-10 additional amino acids at the N- and/or C-terminal end(s). 
     
     
         70 . The method of  claim 68 , wherein the isolated polypeptide consists of 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRSLGHPEPLSNGRP. 
                 
             
                
                
               
            
           
         
       
     
     
         71 . The method of  claim 69 , wherein the isolated polypeptide consists of 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   RRSLGHPEPLSNGRP.