Methods and compositions for modulating neurodegeneration

Abstract

Disclosed are polypeptides and polynucleotides having very long chain fatty acid coA synthetase activity. The polypeptides and polynucleotides are useful in identifying and modulating neurodegeneration.

What is claimed is:  
     
         1 . An isolated polynucleotide consisting of the nucleic acid sequence set forth in SEQ ID NO:1.  
     
     
         2 . An isolated polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:1.  
     
     
         3 . An isolated polynucleotide encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         4 . An isolated polynucleotide encoding a polypeptide the sequence of which comprises the amino acid sequence of SEQ ID NO:2 with 0 to 50 conservative amino acid substitutions, wherein the polypeptide is a very long chain fatty acid acyl (VLCFA) CoA synthetase that converts a very long chain fatty acid to a thioester derivative.  
     
     
         5 . The isolated polynucleotide of  claim 4 , wherein the amino acid sequence comprises 0 to 30 conservative amino acid substitutions.  
     
     
         6 . The isolated polynucleotide of  claim 4 , wherein the amino acid sequence comprises 0 to 10 conservative amino acid substitutions.  
     
     
         7 . An isolated polynucleotide that hybridizes under stringent conditions to a polynucleotide comprising the nucleic acid sequence of SEQ ID NO:1, or complement thereof, wherein the polypeptide is a very long chain fatty acid acyl (VLCFA) CoA synthetase that converts a very long chain fatty acid to a thioester derivative.  
     
     
         8 . An isolated polynucleotide comprising a nucleotide sequence that is at least 80% homologous to the nucleic acid sequence of SEQ ID NO:1, wherein the polypeptide is a very long chain fatty acid acyl (VLCFA) CoA synthetase that converts a very long chain fatty acid to a thioester derivative.  
     
     
         9 . The isolated polynucleotide of  claim 8  comprising a nucleotide sequence that is at least 90% homologous to the sequence of SEQ ID NO:1.  
     
     
         10 . The isolated polynucleotide of  claim 8  comprising a nucleotide sequence that is at least 95% homologous to the sequence of SEQ ID NO:1.  
     
     
         11 . An isolated polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:1, wherein thymine is uridine.  
     
     
         12 . An isolated polynucleotide comprising a sequence that encodes a polypeptide the amino acid sequence of which is at least 80% identical to the sequence of SEQ ID NO:2.  
     
     
         13 . The isolated polynucleotide of  claim 12 , wherein the amino acid sequence is at least 90% identical to the sequence of SEQ ID NO:2.  
     
     
         14 . The isolated polynucleotide of  claim 12 , wherein the amino acid sequence is at least 95% identical to the sequence of SEQ ID NO:2  
     
     
         15 . A vector comprising the polynucleotide of  claim 1 ,  2 ,  3 ,  4 ,  7 ,  8 ,  11  or  12 .  
     
     
         16 . The vector of  claim 12 , wherein the vector is an expression vector.  
     
     
         17 . The vector of  claim 12 , wherein the vector is a plasmid.  
     
     
         18 . The vector of  claim 12 , wherein the vector is a viral vector.  
     
     
         19 . A host cell transformed with the vector of  claim 12 .  
     
     
         20 . The host cell of  claim 16 , wherein the cell is a eukaryotic cell.  
     
     
         21 . The host cell of  claim 16 , wherein the cell is a prokaryotic cell.