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Uses for prevention or treatment of brain diseases using microrna

a brain disease and microrna technology, applied in the field of brain disease prevention or treatment, can solve the problems of loss of memory and intelligence, not being used to cure, and not being able to control the formation of amyloid beta, so as to prevent or treat the disease

Active Publication Date: 2020-12-17
BIORCHESTRA LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present patent is about a pharmaceutical composition and a method for preventing or treating brain diseases using a microRNA called miR-485-3p. The invention provides a pharmaceutical composition containing a miR-485-3p inhibitor and a method for administering it to treat brain diseases. Additionally, the patent describes a method for screening substances that could be used as agents for preventing or treating brain diseases by measuring the expression level of miR-485-3p. The technical effects of this patent are that it provides a novel approach for developing pharmaceutical compositions and screening agents for brain diseases using miR-485-3p inhibitors.

Problems solved by technology

Because these regions of the brain are associated with memory and intelligence, functional deficit in these regions may cause loss of memory and intelligence.
Despite their effectiveness in preventing further destructive progress of this disease, they are not used to cure the disease.
However, because the process of amyloid beta formation has not been fully elucidated scientifically, it is not yet possible to control the formation of amyloid beta.
Thus, various factors involved in this cleavage reaction (e.g., inflammation reaction, etc.) increase the phosphorylation of tau protein, and also increase the accumulation of paired helical filaments (PHF) in combination with NFT, resulting in damage to the nerve.
Despite the biological knowledge about the disease, clinical application is still not successful.

Method used

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  • Uses for prevention or treatment of brain diseases using microrna
  • Uses for prevention or treatment of brain diseases using microrna
  • Uses for prevention or treatment of brain diseases using microrna

Examples

Experimental program
Comparison scheme
Effect test

example 2

of miR-485-3p Expression in Hippocampus and Cerebral Cortex of 5×FAD Mouse (RT-qPCR)

[0119](1) Research Methods

[0120]The 5×FAD transgenic mouse is an animal model of Alzheimer disease obtained by overexpressing mutant forms of APP and PSEN1, which exhibits severe accumulation of intraneuronal Aβ42 from about 6 weeks.

[0121]Given the results of Example 1, RT-qPCR was performed to confirm the expression of miR-485-3p in the dementia animal model. 5×FAD transgenic mice and wild-type (WT) mice were deeply anesthetized and sacrificed by decapitation. After excising the brain immediately, the hippocampus and cerebral cortex were dissected from the remaining brain structure. Total miRNA was isolated from the hippocampus using the PAXgene Tissue miRNA kit (Qiagen, USA) according to the manufacturer's instructions. cDNA was synthesized using the miScript II RT kit (Qiagen, USA), and qPCR was performed using the mmu_miR-485-3p miScript Primer Assay kit and the miScript SYBR Green PCR kit. The m...

example 3

n of Target Gene of miR-485-3p

[0124]In order to analyze the base sequence and target location of hsa-miR-485-3p, it was confirmed using a target prediction software (miRDB) that the 3′-untranslated region (UTR) of human-derived ELAVL2 is the target of hsa-miR-485-3p. It was confirmed that the identified seed sequence was conserved also in mmu-miR-485-3p and the 3′-untranslated region of mouse-derived ELAVL2.

[0125]FIG. 4 shows a list of the 3′-untranslated region (UTR) mRNAs of ELAVL2, and shows the target 3′-untranslated region (UTR) mRNAs of miR485-3p. The 5′ seed sequence of miR-485-3p (ELAVL2) is shown in blue color. Table 4 shows the base sequence and target location of mmu-miR485-3p. It was confirmed using a target prediction software (miRDB) that the 3′-untranslated region (UTR) of human-derived ELAVL2 is the target of mmu-miR-485-3p.

TABLE 4Analysis of base sequence and target location of mrnu-miR485-3pGeneSequence (5′ → 3′)mmu-miR-485-3pAGUCAUACACGGCUCUCCUCUCSEQ ID NOTargetTo...

example 4

ion of Expression of Amyloid Beta (Aβ) 42 and ELAVL2 in Hippocampus and Cerebral Cortex of 5×FAD Mouse

[0126](1) Research Methods

[0127]Given the results of Example 3, the expression of Aβ 42 and ELAVL2 in the hippocampus and the cerebral cortex of 5×FAD was investigated. After sacrificing an anesthetized mouse by decapitation, the brain was extracted immediately. After preparing a homogenate of the brain (hippocampus and cerebral cortex), western blot was conducted using anti-ELAVL2 antibody (Abcam, USA). The immunoreactive protein was visualized with a chemiluminescence reagent (GE Healthcare, UK) and was measured and quantified using a chemiluminescence analyzer (Fusion SL). Aβ 42 in the hippocampus and the cerebral cortex was quantified by using the mouse / rat amyloid beta (1-42) ELISA kit (IBL) according to the manufacturer's instructions.

[0128](2) Research Results

[0129]1) Confirmation of Aβ 42 Expression in Hippocampus and Cerebral Cortex

[0130]FIGS. 5A-5B show results of quantita...

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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.

Description

[0001]The content of the electronically submitted sequence listing in ASCII text file (Name: 4366_0120000_SeqListing_ST25.txt; Size: 1,985 bytes; and Date of Creation: Jun. 13, 2019) filed with the application is herein incorporated by reference in its entirety.TECHNICAL FIELD[0002]The present disclosure relates to a use of miR-485-3p 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.BACKGROUND OF THE DISCLOSURE[0003]Alzheimer's disease is the most common form of dementia. 75% of patients with dementia have Alzheimer's disease. In most cases, Alzheimer's disease begins in people over 65 years of age, although it can occur earlier in rare cases. In the United States, about 3% of the population aged 65-74 years, ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N15/113A61P25/28
CPCA61P25/28C12N2310/321C12N15/113C12N2310/113C12N2310/3521
Inventor RYU, JIN-HYEOBCHO, HYUN-JEONG
Owner BIORCHESTRA LTD