Activity dependent neurotrophic factor iii (adnf iii)

Abstract

The present invention relates generally to Activity Dependent Neurotrophic Factor III (ADNF III), also known as Activity Dependent Neuroprotective Protein (ADNP). More particularly, the present invention relates to nucleic acid sequences encoding ADNF III polypeptides; ADNF III polypeptides encoded by such nucleic acid sequences; antibodies to ADNF III polypeptides; and methods of using such ADNF III polypeptides for the treatment of neurological deficiencies and for the prevention of cell death associated with (1) gp120, the envelope protein from HIV; (2) N-methyl-D-aspartic acid (excito-toxicity); (3) tetrodotoxin (blockage of electrical activity); and (4) β-amyloid peptide, a substance related to neuronal degeneration in Alzheimer's disease.

1 - 55 . (canceled) 
     
     
         56 . A method for preventing neuronal cell death, said method comprising contacting said neuronal cells with an Activity Dependent Neurotrophic Factor (ADNF) III polypeptide in an amount sufficient to prevent neuronal cell death, wherein the ADNF III polypeptide comprises the following amino acid sequence: 
       
         
           
                 
                 
               
                   (SEQ ID NO:10) 
                     
                 
                 
                 
                 
               
                     
                   (R 1 ) x -Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln-(R 2 ) y   
                     
                 
             
                
               
            
             
                
               
            
           
         
       
       and conservatively modified variations thereof, in which:
 R 1  is an amino acid sequence comprising from 1 to about 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs; 
 R 2  is an amino acid sequence comprising from 1 to about 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs; and 
 x and y are independently selected and are equal to zero or one. 
 
     
     
         57 . The method of  claim 56 , wherein x and y are both zero. 
     
     
         58 . A method for treating a neurodegenerative pathology in a subject in need of such treatment, the method comprising administering to the subject a pharmaceutically acceptable carrier and an Activity Dependent Neurotrophic Factor (ADNF) III polypeptide in an amount sufficient to prevent neuronal cell death associated with the neurodegenerative pathology, wherein the ADNF III polypeptide comprises the following amino acid sequence: 
       
         
           
                 
                 
               
                   (SEQ ID NO:10) 
                     
                 
                 
                 
                 
               
                     
                   (R 1 ) x -Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln-(R 2 ) y   
                     
                 
             
                
               
            
             
                
               
            
           
         
       
       and conservatively modified variations thereof, in which:
 R 1  is an amino acid sequence comprising from 1 to about 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs; 
 R 2  is an amino acid sequence comprising from 1 to about 40 amino acids wherein each amino acid is independently selected from the group consisting of naturally occurring amino acids and amino acid analogs; and 
 x and y are independently selected and are equal to zero or one. 
 
     
     
         59 . The method of  claim 58 , wherein x and y are both zero. 
     
     
         60 . The method of  claim 58 , wherein the neurodegenerative pathology is a member selected from the group consisting of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), a neurodegenerative pathology associated with aging, a pathological change resulting from a focal trauma, peripheral neuropathy, retinal neuronal degeneration, and dopamine toxicity. 
     
     
         61 . The method of  claim 60 , wherein the neurodegenerative pathology is a neurodegenerative pathology associated with aging and is degeneration of a cerebellar neuron or a cortical neuron. 
     
     
         62 . The method of  claim 60 , wherein the neurodegenerative pathology is a pathological change resulting from a focal trauma and the focal trauma is a member selected from the group consisting of stroke, focal ischemia, hypoxic-ischemic encephalopathy, closed head trauma and direct trauma.