Mutated tau protein fragment and use thereof

Abstract

A mutated tau protein fragment and a use thereof are disclosed. The mutated tau protein fragment consists 12 amino acid residues and thus can easily be prepared. In addition, when the mutated tau protein fragment is injected into an individual as an antigen, a neutralizing antibody against the mutated tau protein is generated. Moreover, the mutated tau protein fragment reduces the aggregation of abnormal tau proteins. Accordingly, the mutated tau protein fragment can be effectively used for the prevention or treatment of degenerative neurological diseases.

1 . An antibody capable of specifically binding to a modified tau protein fragment consisting of the following sequence of 12 consecutive amino acid residues:
 Val-Gln-Ile-Ile-Asn-Lys-Lys-Leu-Asp-Leu-Ser-Asn (SEQ ID NO: 1) where lysine at position 6 of SEQ ID NO: 1 is acetylated,   or an antigen-binding fragment thereof.   
     
     
         2 . The antibody or an antigen-binding fragment thereof of  claim 1 , wherein the antigen-binding fragment is any one selected from the group consisting of Fab, scFv, F(ab) 2 , and Fv. 
     
     
         3 . A recombinant expression vector comprising a nucleotide sequence encoding the antibody or a fragment thereof of  claim 1 . 
     
     
         4 . A recombinant host cell transformed with the vector of  claim 3 . 
     
     
         5 . The recombinant host cell of  claim 4 , wherein the host cell is a prokaryotic or eukaryotic cell. 
     
     
         6 . The recombinant host cell of  claim 5 , wherein the prokaryotic cell is  E. coli  or yeast. 
     
     
         7 . The recombinant host cell of  claim 6 , wherein the eukaryotic cell is an NS/0 myeloma cell, a 293 cell, a Chinese hamster ovary cell (CHO cell), a HeLa cell, a CapT cell (human amniotic fluid-derived cell), or a COS cell. 
     
     
         8 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of  claim 1  as an active ingredient and a pharmaceutically acceptable salt thereof. 
     
     
         9 . A diagnostic kit for a degenerative nerve disease, comprising the antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         10 . A method for providing information on a degenerative neurological disease, the method comprising:
 i) a step of measuring an expression level of a modified tau protein, in which the 280 th  amino acid is acetylated, in a test sample isolated from a subject suspected of having a degenerative neurological disease;   ii) a step of comparing the measured expression level of the modified tau protein of step i) with an expression level of the modified tau protein in a normal control sample; and   iii) a step of determining that in a case where the expression level of the modified tau protein is higher than that in the control, the individual has a high probability of developing the degenerative neurological disease,   wherein the measuring expression level of the modified tau protein in step 1) comprises contacting the test sample with the antibody or antigen-binding fragment thereof of  claim 1 .   
     
     
         11 . A method for preventing or treating a degenerative neurological disease, comprising a step of administering a composition to an individual who is expected to develop the degenerative neurological disease or has developed the degenerative neurological disease, wherein the composition the antibody or antigen-binding fragment thereof of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the degenerative neurological disease is a tau protein-mediated neurological disease. 
     
     
         13 . The method of  claim 9 , wherein the tau protein-mediated neurological disease is primary age-related tauopathy, chronic traumatic encephalopathy, progressive supranuclear palsy, progressive supranuclear palsy, corticobasal degeneration, Lytico-Bodig disease, Parkinsonism, subacute sclerosing meningitis, lead encephalopathy, tuberous sclerosis, ganglioglioma, gangliocytoma, meningioangiomatosis, subacute sclerosing panencephalitis, Hallervorden-Spatz disease, or lipofuscinosis. 
     
     
         14 . The method of  claim 13 , wherein the tauopathy is Alzheimer's disease (AD), Pick's disease (PiD), a group of related disorders collectively referred to as frontotemporal dementia (FTDP-17) with Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis (ALS), Creutzfeld-Jakob disease (CJD), boxer dementia (DP), Gerstmann-Sträussler-Scheinker disease (GSSD), Lewy body disease, chronic traumatic encephalopathy (CTE), spinal cord injury, epilepsy, or Huntington's disease.