Peptides for the regulation of neurotransmitter sequestration and release

Abstract

A method of selecting an agent comprising a neuroprotecting activity is disclosed. The method comprises: (a) introducing a plurality of agents into a plurality of cells; and (b) analyzing Vesicular Monoamine Transporter 2 (VMAT2) transcription in the cells; and (c) identifying an agent of the plurality of agents capable of up-regulating DJ-1-dependent VMAT2 transcription in the cells, thereby selecting the agent comprising the neuroprotecting activity.

What is claimed is: 
     
         1 . A method of selecting an agent comprising a neuroprotecting activity, the method comprising:
 (a) introducing a plurality of agents into a plurality of cells;   (b) analyzing Vesicular Monoamine Transporter 2 (VMAT2) transcription in said cells; and   (c) identifying an agent of the plurality of agents capable of up-regulating DJ-1-dependent VMAT2 transcription in said cells, thereby selecting the agent comprising the neuroprotecting activity.   
     
     
         2 . The method of  claim 1 , wherein the agent is a peptide agent. 
     
     
         3 . The method of  claim 1 , wherein the agent is a small molecule. 
     
     
         4 . The method of  claim 2 , wherein said peptide agent comprises a DJ-1 sequence. 
     
     
         5 . The method of  claim 1 , wherein said cell is a neuronal cell. 
     
     
         6 . The method of  claim 5 , wherein said neuronal cell is a neuroblastoma cell. 
     
     
         7 . The method of  claim 1 , wherein said analyzing is effected by determining an interaction between the agent and a promoter region of a Vesicular Monoamine Transporter 2 (VMAT2) polynucleotide. 
     
     
         8 . The method of  claim 1 , wherein said analyzing is effected by a transcription assay. 
     
     
         9 . The method of  claim 8 , wherein said transcription assay is a reporter based assay. 
     
     
         10 . The method of  claim 7 , wherein said promoter region of VMAT2 is endogenous to said cell. 
     
     
         11 . The method of  claim 7 , wherein said promoter region of VMAT2 is exogenous to said cell. 
     
     
         12 . The method of  claim 11 , wherein said promoter region is transcriptionally linked to a detectable polypeptide. 
     
     
         13 . An agent identified according to the method of  claim 1 . 
     
     
         14 . The agent of  claim 13 , being a peptide agent. 
     
     
         15 . An isolated peptide or peptide mimetic thereof, comprising an amino acid sequence which regulates VMAT2 transcription, the peptide being no more than 30 amino acids in length. 
     
     
         16 . An isolated peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-6, 17-526 and 527. 
     
     
         17 . An isolated polynucleotide comprising a nucleic acid sequence encoding the peptide of  claim 14 . 
     
     
         18 . An isolated polynucleotide comprising a nucleic acid sequence encoding the peptide of  claim 16 . 
     
     
         19 . A method of treating a neurodegenerative disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of the isolated peptide of  claim 16 , thereby treating the neurodegenerative disorder. 
     
     
         20 . A method of treating a neurodegenerative disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of the isolated polynucleotide of  claim 18 , thereby treating the neurodegenerative disorder. 
     
     
         21 . A method of increasing viability of neuronal cells, the method comprising contacting the neuronal cells with an agent selected according to the method of  claim 1 , thereby increasing viability of the neuronal cells. 
     
     
         22 . A method of selecting an agent comprising a neurotoxic activity, the method comprising:
 (a) introducing agents into a cell;   (b) analyzing Vesicular Monoamine Transporter 2 (VMAT2) transcription in said cell; and   (c) identifying the agent capable of down-regulating DJ-1-dependent VMAT2 transcription in said cell, thereby selecting the agent comprising the neurotoxic activity.   
     
     
         23 . A method of decreasing viability of neuronal cells, the method comprising contacting the neuronal cells with an agent selected according to the method of  claim 22 , thereby decreasing viability of the neuronal cells.