Amidated Dopamine Neuron Stimulating Peptides for CNS Dopaminergic Upregulation

Abstract

The present invention relates to novel proteins, referred to herein as amidated glial cell line-derived neurotrophic factor (GDNF) peptides (or “Amidated Dopamine Neuron Stimulating peptides (ADNS peptides)”), that are useful for treating brain diseases and injuries that result in dopaminergic deficiencies.

1 . A method for reducing apoptosis of a neuron by delivering to the neuron a composition comprising at least one of the following peptides:
 (a) a purified Amidated Dopamine Neuron Stimulating peptide (ADNS peptide) comprising the amino acid sequence ERNRQAAAANPENSRGK-amide (SEQ ID NO: 2);   (b) a purified ADNS peptide comprising the amino acid sequence FPLPA-amide (SEQ ID NO: 3); and   (c) a purified ADNS peptide comprising the amino acid sequence PPEAPAEDRSL-amide (SEQ ID NO: 4)   wherein the composition comprises an amount of the ADNS peptide sufficient to reduce apoptosis, as evidenced by an increase in GAPDH localization in the cytosol or membrane and/or as evidenced by a reduction in capase-3 activity and/or restoration of mitochondrial membrane potential and/or reduction of cytochrome c release from mitochondria in the neuron after the peptide is delivered to the neuron.   
     
     
         2 . The method of  claim 1  wherein the composition comprises a purified ADNS peptide comprising the amino acid sequence PPEAPAEDRSL-amide (SEQ ID NO: 4). 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the ADNS peptide is a purified ADNS peptide comprising the amino acid sequence ERNRQAAAANPENSRGK-amide (SEQ ID NO: 2). 
     
     
         8 . The method of  claim 1 , wherein the ADNS peptide is a purified ADNS peptide comprising the amino acid sequence FPLPA-amide (SEQ ID NO: 3). 
     
     
         9 . The method of  claim 7  wherein the amount of ADNS peptide sufficient to reduce apoptosis is determined by detecting an increase in GAPDH localization in the cytosol or membrane after the cells are contacted with the peptide.