Uses for prevention or treatment of brain diseases using microrna

Abstract

The present disclosure relates to a pharmaceutical composition for preventing or treating a brain disease, more particularly to a pharmaceutical composition for preventing or treating a brain disease, which contains a miR-485-3p inhibitor, and a method for screening an agent for preventing or treating a brain disease, which includes a step of measuring the expression level of miR-485-3p. Because the composition for treating a brain disease, which contains a miR-485-3p inhibitor, can restore the ELAVL2 protein unlike the exiting therapeutic agents for Alzheimer's disease, which are limited only to alleviating symptoms by inducing decreased expression of amyloid beta 42, the present disclosure can fundamentally treat various diseases caused by decreased expression of ELAVL2, such as Alzheimer's disease, autism spectrum disorder, mental retardation, amyotrophic lateral sclerosis, etc. Therefore, the present disclosure is useful for treating brain diseases including Alzheimer's disease fundamentally.

1 . A method of preventing or treating a brain disease in a subject in need thereof comprising administering a miR-485-3p inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the miR-485-3p inhibitor inhibits the expression of miR-485-3p or inhibits the interaction between miR-485-3p and the 3′-UTR of ELAVL2 (ELAV-like RNA binding protein 2). 
     
     
         3 . The method of  claim 1 , wherein the miR-485-3p inhibitor is a nucleic acid molecule binding to all or a part of the base sequence of SEQ ID NO 1 or SEQ ID NO 2. 
     
     
         4 . The method of  claim 3 , wherein the nucleic acid molecule is selected from a group consisting of a DNA, an RNA, an antagomir, a siRNA, a shRNA and an oligonucleotide. 
     
     
         5 . The method of  claim 3 , wherein the nucleic acid molecule is an antisense oligonucleotide comprising a sequence partially or completely complementary to the base sequence of SEQ ID NO 1. 
     
     
         6 . The method of  claim 5 , wherein the antisense oligonucleotide is represented by a base sequence selected from SEQ ID NO 3 through SEQ ID NO 7. 
     
     
         7 . The method of  claim 5 , wherein the antisense oligonucleotide comprises one or more modification selected from: 1) modification to a LNA (locked nucleic acid) or PNA (peptide nucleic acid) form; 2) substitution of the —OH group at the 2′ carbon of a nucleotide with —CH 3  (methyl); and 3) modification of a nucleotide bond to phosphorothioate. 
     
     
         8 . The method of  claim 1 , wherein the miR-485-3p inhibitor has one or more of the following features: 1) recovery of the expression level of ELAVL2; 2) inhibition of the production of amyloid beta 42 (Aβ42); 3) inhibition of the expression of amyloid precursor protein (APP); and 4) inhibition of the phosphorylation of tau protein. 
     
     
         9 . The method of  claim 1 , wherein the brain disease is selected from a group consisting of Alzheimer's disease, autism spectrum disorder, mental retardation, amyotrophic lateral sclerosis, seizure, stroke, Parkinson's disease and spinal cord injury. 
     
     
         10 . The method of  claim 1 , wherein the composition is formulated into a formulation for any of intranasal administration, intravenous administration, subcutaneous injection, intrathecal injection, inhalation administration or oral administration. 
     
     
         11 . A method for screening an agent for preventing or treating a brain disease, which comprises:
 (A) treating a cell expressing miR-485-3p with a candidate substance and measuring the expression level of miR-485-3p; and   (B) screening the candidate substance as an agent for preventing or treating a brain disease if the expression level of miR-485-3p measured in the step (A) is decreased as compared to a control group not treated with the candidate substance.   
     
     
         11 - 12 . (canceled) 
     
     
         13 . The method of  claim 11 , wherein the activity of the miR-485-3p is determined by analyzing the interaction between the miR-485-3p and the 3′-UTR of ELAVL2 (ELAV-like RNA binding protein 2). 
     
     
         14 . The method of  claim 11 , wherein the brain disease is selected from a group consisting of Alzheimer's disease, autism spectrum disorder, mental retardation, amyotrophic lateral sclerosis, seizure, stroke, Parkinson's disease and spinal cord injury. 
     
     
         15 . A composition comprising a miR-485-3p inhibitor and a pharmaceutically acceptable excipient. 
     
     
         16 . The composition of  claim 15 , wherein the miR-485-3p inhibitor inhibits the expression of miR-485-3p or inhibits the interaction between miR-485-3p and the 3′-UTR of an ELAV-like RNA binding protein 2 (ELAVL2). 
     
     
         17 . A method of increasing an expression level of an ELAV-like RNA binding protein 2 (ELAVL2) in a subject in need thereof, comprising administering the composition of  claim 15  to the subject. 
     
     
         18 . A method of decreasing an expression level of a β-amyloid peptide in a subject in need thereof, comprising administering the composition of  claim 15  to the subject. 
     
     
         19 . A method of reducing a phosphorylation of a tau protein in a subject in need thereof, comprising administering the composition of  claim 15  to the subject. 
     
     
         20 . A method of increasing a cognitive function in a subject in need thereof, comprising administering the composition of  claim 15  to the subject.