Biomarker for parkinson's disease and use thereof

Abstract

An antibody has as a target molecule a ubiquitin protein comprising a phosphorylated serine residue at position 65. In addition, a method is provided for specifically detecting Parkinson's disease at an early stage, in which a target molecule is a ubiquitin protein comprising a phosphorylated serine residue at position 65, a pharmaceutical composition for definitively treating or preventing Parkinson's disease, and a method for screening for the pharmaceutical composition.

1 . A ubiquitin protein comprising a phosphorylated serine residue at position 65 (SEQ ID NO:1), or a ubiquitin protein consisting of an amino acid sequence comprising a substitution, deletion, insertion and/or addition of 1 to 3 amino acids with respect to the amino acid sequence shown in SEQ ID NO:1, on condition that the phosphorylated serine residue at position 65 is conserved. 
     
     
         2 . A phosphorylation-mimicking form of ubiquitin, in which the serine residue at position 65 is substituted with an aspartic acid residue (SEQ ID NO:2), or a phosphorylation-mimicking form of ubiquitin consisting of an amino acid sequence comprising a substitution, deletion, insertion and/or addition of 1 to 3 amino acids with respect to the amino acid sequence shown in SEQ ID NO:2, on condition that the aspartic acid residue at position 65 is conserved. 
     
     
         3 . A method for testing for Parkinson's disease, comprising a step of detecting or quantifying a ubiquitin protein comprising a phosphorylated serine residue at position 65 in a sample isolated from a subject. 
     
     
         4 . The method according to  claim 3 , wherein the step of detecting or quantifying is carried out by an immunological technique. 
     
     
         5 . A biomarker for detecting Parkinson's disease, which consists of a ubiquitin protein comprising a phosphorylated serine residue at position 65. 
     
     
         6 . A therapeutic agent or a preventive agent for Parkinson's disease, which comprises a ubiquitin protein comprising a phosphorylated serine residue at position 65. 
     
     
         7 . A therapeutic agent or a preventive agent for Parkinson's disease, which comprises a phosphorylation-mimicking form of ubiquitin in which the serine residue at position 65 is substituted with an aspartic acid residue. 
     
     
         8 . A method for screening for a therapeutic agent or a preventive agent for Parkinson's disease, which comprises:
 (1) a step of providing cells that express PINK1;   (2) a step of damaging mitochondria in the cells;   (3) a step of contacting the cells with a candidate compound; and   (4) a step of measuring the amount of a ubiquitin protein comprising a phosphorylated serine residue at position 65, which has been generated in the cells.   
     
     
         9 . A method for screening for a therapeutic agent or a preventive agent for Parkinson's disease, which comprises:
 (1) a step of preparing a phosphorylation reaction solution containing a ubiquitin protein, a kinase, and a phosphate donor;   (2) a step of adding a candidate compound to the phosphorylation reaction solution; and   (3) a step of measuring the amount of a ubiquitin protein comprising a phosphorylated serine residue at position 65, which has been generated in the phosphorylation reaction solution.   
     
     
         10 . The method according to  claim 9 , wherein the phosphorylation reaction solution is a cell extract.