KR20200009340A - Pharmaceutical composition and Health-functional food for preventing or treating Neurological disorders - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating peripheral nerve diseases and health functional food for preventing or alleviating peripheral nerve diseases, wherein the pharmaceutical composition and the health functional food contain an oligonucleotide consisting of a sequence listing of SEQ ID NO: 1, effectively inhibiting the expression of EGR2. The pharmaceutical composition containing the oligonucleotide can obtain an effect of preventing or treating peripheral nerve diseases and the health functional food containing the oligonucleotide can obtain an effect of preventing or alleviating peripheral nerve diseases.

Description

Pharmaceutical composition and health functional food for preventing or treating neurological disorders

The present invention relates to a pharmaceutical composition for preventing or treating peripheral neurological diseases and to health functional foods for prevention or improvement.

Untranslated RNA, microRNA (microRNA) has been known as a powerful regulator of cell phenotype, function and fate through transcriptional and epigenetic regulation. MicroRNA genes are transcribed by RNA polymerase II to become large primary transcripts (pri-microRNAs), and pri-microRNAs become precursor microRNAs (pre-microRNAs) of about 70 nt in length by protein complexes including RNase III enzyme Drosha. . The pre-microRNA migrates to the cytoplasm and becomes about 22 nt mature microRNA by the second RNase III enzyme, DICER. Mature microRNA enters ribonuclear particles and becomes RISC, an RNA-induced silencing complex, where gene silencing occurs by binding microRNA to target sites of mRNA and inhibiting translation or degradation of target mRNA. MicroRNAs are known to be involved in cell cycle regulation, apoptosis, developmental and physiological stages. It is also involved in stem cell differentiation, hematopoietic action, hypoxia, development of myocardium and skeletal muscle, neurogenesis, insulin secretion, cholesterol metabolism, aging, immune responses and viral proliferation. During embryonic embryogenesis, microRNAs are expressed in tissues or at specific times, indicating that microRNAs also play a role in differentiation and tissue specificity. MicroRNAs induce gene silencing by binding to target sites in the 3 ′ UTR of the target mRNA, inhibiting protein synthesis or causing degradation of the mRNA. Since most target sites in mRNA are only partially complementary to microRNA sequences, one microRNA can regulate several different mRNAs. In addition, one mRNA may have multiple binding sites for multiple microRNAs, resulting in complex gene regulation relationships. In addition, many microRNAs are part of a very similar microRNA family. As described above, miRNA is involved in various gene expressions and at the same time is involved in various metabolic regulatory processes including adipocyte differentiation, metabolic integration, and appetite regulation. As a result, it is highly probable to apply miRNA as a therapeutic candidate for metabolic diseases and is a promising field for development as a therapeutic agent.

Korea Patent 1815734

The present invention relates to an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1, an object of the present invention to provide a pharmaceutical composition for preventing or treating peripheral neurological disease and a health functional food for prevention or improvement.

1. A pharmaceutical composition for preventing or treating peripheral neuropathy disease comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1.

2. In the above 1, wherein the peripheral neuropathy is acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, diabetic peripheral neuropathy, vasculitis neuropathy, hereditary peripheral neuropathy, Charco Maritus disease, At least one selected from the group consisting of degerin sotas disease and congenital hypomyelinated neuropathy.

3. The composition according to the above 1, wherein the peripheral neuropathy is at least one selected from the group consisting of Charcoal Maritus disease, degerin sotas disease and congenital hypomyelinated neuropathy.

4. A health functional food for preventing or improving peripheral neuropathy disease comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1.

5. In the above 4, wherein the peripheral neuropathy is acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, diabetic peripheral neuropathy, vasculitis neuropathy, hereditary peripheral neuropathy, Charco Maritus disease, Health functional food which is at least one selected from the group consisting of degerin sotas disease and congenital hypomyeloma.

6. In the above 4, wherein the peripheral neurological disease is at least one selected from the group consisting of Charcoal Maritus disease, degerin sotas disease and congenital hypomyeloma neuropathy.

The present invention relates to an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1, in the case of a pharmaceutical composition comprising the same for the prevention or treatment of peripheral neurological disease, in the case of health functional food comprising the same for the prevention or improvement of peripheral neurological disease The effect can be obtained.

Figure 1 shows the expression of EGR2 after transfection of 6 miRNAs (microRNA 152-3p, miRNA 148b-3p, miRNA 20a-5p, miRNA 150-5p, miRNA 137-3p, miRNA 137-3p) into Schwann cells, which are peripheral nerve cells. It is a figure which shows that only the miRNA of this invention inhibits expression of EGR2 significantly.
2 is a measure of the extent to which miRNAs inhibit the UTR of EGR2, a major neuronal differentiation marker, and shows that the miRNA of the present invention significantly inhibits UTR of EGR2.
3 is a diagram confirming whether the miRNA of the present invention is inhibited in the differentiation of rats using rats.
4 is a diagram showing the expression of the miRNA of the present invention after peripheral nerve injury using a mouse.

Definitions of terms used in the present invention are as follows.

"Nucleic acid" is meant to include any DNA or RNA, such as chromosomes, mitochondria, viruses and / or bacterial nucleic acids present in tissue samples. One or both strands of a double-stranded nucleic acid molecule and any fragment or portion of an intact nucleic acid molecule.

"Gene" means any nucleic acid sequence or portion thereof that has a functional role in protein coding or transcription or in the regulation of other gene expression. The gene may consist of any nucleic acid encoding a functional protein or only a portion of a nucleic acid encoding or expressing a protein. Nucleic acid sequences can include gene abnormalities in exons, introns, initiation or termination regions, promoter sequences, other regulatory sequences, or unique sequences adjacent to genes.

The term "gene expression" generally refers to a cellular process in which a biologically active polypeptide is produced from a DNA sequence and exhibits biological activity in a cell. In that sense, gene expression includes not only transcriptional and translational processes, but also post-transcriptional and posttranslational processes that can affect the biological activity of a gene or gene product. The processes include, but are not limited to, RNA synthesis, processing and transport, as well as post-translational modifications of the polypeptide synthesis, transport and polypeptide. In the case of genes that do not encode protein products, such as miRNA genes, the term "gene expression" refers to the process by which precursor miRNAs are produced from a gene. Typically, this process is referred to as transcription, although unlike transcription induced by RNA polymerase II for a protein coding gene, the transcription product of the miRNA gene is not translated to produce a protein. Nevertheless, generation of mature miRNA from miRNA genes is encompassed by the term "gene expression" as that term is used herein.

"miR" or "microRNA" refers to 21-23 non-coding RNAs that regulate gene expression after transcription by promoting degradation of target RNA or inhibiting their translation. As used herein, the mature sequence of miRNA can be obtained from the miRNA database (http://www.mirbase.org). Generally, microRNAs are transcribed into precursors of about 70-80 nt (nucleotide) in length with a hairpin structure called pre-miRNA, and are then cut and matured by Dicer, an RNAse III enzyme. MicroRNAs form ribonucleocomplexes called miRNPs that cleave target genes through complementary binding to target sites or inhibit translation. More than 30% of human miRNAs are present in clusters, transcribed into one precursor, and cleaved to form the final mature miRNA.

The term "target gene" refers to a gene that is targeted for regulation using the methods and compositions of the subject matter disclosed herein. Therefore, the target gene comprises a nucleic acid sequence whose expression level is down regulated by miRNA at the mRNA or polypeptide level. Similarly, the term "target RNA" or "target mRNA" refers to a transcript of a target gene to which miRNA binds to induce regulation of expression of the target gene.

The term "transcription" refers to a cellular process that involves the interaction of an RNA polymerase with a gene that induces expression as RNA of structural information present in the coding sequence of the gene.

The expression “down-regulation” refers to the expression of specific genes in mRNA or the expression of proteins in activated cells by intracellular transcription or translation in activated cells, compared to normal tissue cells. Means reduced.

"Treatment" means an approach to obtain beneficial or desirable clinical results. For the purposes of the present invention, beneficial or desirable clinical outcomes include, but are not limited to, alleviation of symptoms, reduction of disease range, stabilization of disease state (ie, not worsening), delay or slowing of disease progression, disease state Improvement or temporary mitigation and alleviation (partially or wholly), detectable or not detected. "Treatment" may also mean increasing survival compared to expected survival when untreated. Treatment refers to both therapeutic treatment and prophylactic or preventive measures. Such treatments include not only the disorders to be prevented but also the treatments required for already occurring disorders.

"Prevention" means any action that inhibits or delays the development of a related disease. It will be apparent to those skilled in the art that the compositions herein can prevent the initial symptoms, or related diseases, if administered before they appear.

Hereinafter, the present invention will be described in detail.

The present invention provides a pharmaceutical composition for preventing or treating peripheral neuropathy disease comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1.

Oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 (miRNA) of the present invention targets the EGR2 (Early growth response protein 2) gene for the prevention or treatment of peripheral neurological diseases.

The Early Growth Response 2 (EGR2) gene (SEQ ID NO: 2) is one of a group of EGR genes consisting of EGR 1,2,3,4, and the EGR protein encoded by the EGR gene is a group of early early genes. One. EGR transcription factors are expressed at high levels in a broad range of areas, including the frontal lobe, hippocampus, and striatum in the brain, and are rapidly induced by various neuropsychological stimulation treatments, including stress, new environment, antipsychotic drugs, and electroconvulsive shock. It is suggested as one of the underlying changes in causing long-term neurological changes in the brain. In particular, EGR transcription factors play a major role in nervous system activity and structural regulation by directly involved in the transcription of various transcription factors, cytoskeletal proteins, phosphorylation-dephosphorase, ubiquitin-related protein disruption proteasome-related proteins. EGR2 plays an important role, in particular, in the myelination of peripheral nerves and in the development of the posterior brain, and functions as a marker critical for the differentiation of peripheral nerve cells.

Oligonucleotides consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention are animals including humans, such as monkeys, pigs, horses, cows, sheeps, dogs ), Cats, mice, rabbits, and the like, and preferably human-derived.

The oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention is a functional equivalent of the nucleic acid molecule constituting the same, for example, the deletion of some nucleotide sequences of the oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention , But is modified by substitution or insertion, but includes a variant that can function functionally identical to an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention.

In addition, the oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention may exist in the form of a single strand or a double strand. While mature miRNA molecules exist predominantly single stranded, precursor miRNA molecules are predominantly at least partially self-complementary (eg stem- and loop-structures) that can form double stranded portions. In addition, the oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention may be formed in the form of RNA, DNA, peptide nucleic acids (PNA) or locked nucleic acid (LNA).

Oligonucleotides consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention may be isolated or prepared using standard molecular biology techniques, such as chemical synthesis or recombinant methods, or may be commercially available. In addition, the composition of the present invention is not only the oligonucleotide itself consisting of the nucleotide sequence of SEQ ID NO: 1, but also other substances that can increase the expression rate of the oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention in a cell, for example For example, compounds, natural products, novel proteins, and the like.

On the other hand, oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention may be provided included in the vector for expression in the cell.

Oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention can be introduced into cells using a variety of transformation techniques, such as complexes of DNA and DEAE-dextran, complexes of DNA and nuclear proteins, complexes of DNA and lipids. For this purpose, the oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention may be in a form contained in the carrier to enable efficient introduction into the cell. The carrier is preferably a vector, and both viral and non-viral vectors can be used. As a viral vector, for example, lentiviruses, retroviruses, adenoviruses, adenoviruses, herpesviruses, and abipoxvirus vectors may be used. Preferably is a lentiviral vector, but is not limited thereto. Lentiviruses are a type of retrovirus that infects dividing as well as dividing cells due to the nucleophilicity of a pre-integrated complex (virus "shell") that enables active introduction into the nucleopore or the complete nuclear membrane. There are features that can be made.

In addition, the vector containing the oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention preferably further comprises a selection marker. In the present invention, the term "selection marker" is intended to facilitate selection of transformed cells by introducing an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention. The selectable markers that can be used in the vector are not particularly limited as long as they are genes capable of easily detecting or measuring the introduction of the vector, but typically, drug resistance, nutritional requirements, resistance to cytotoxic agents, or surface proteins. Markers that confer a selectable phenotype, such as expression, for example GFP (green fluorescent protein), puromycin, Neomycin (Neo), hygromycin (Hyg), histidinol dihydro Genase (histidinol dehydrogenase gene: hisD) and guanine phosphosribosyltransferase (Gpt), and the like, and preferably GFP (green fluorescent protein) and puromycin markers can be used.

On the other hand, a prophylactic or therapeutic pharmaceutical composition comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention may further include a pharmaceutically acceptable carrier, it may be formulated with a carrier. As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not stimulate the organism and does not inhibit the biological activity and properties of the administered compound. Acceptable pharmaceutical carriers in compositions formulated in liquid solutions are sterile and biocompatible, which include saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

The composition of the present invention is applicable to any formulation comprising an oligonucleotide consisting of the base sequence of SEQ ID NO: 1 as an active ingredient of the present invention, can be prepared in oral or parenteral formulations. Pharmaceutical formulations of the present invention may be oral, rectal, nasal, topical (including the cheek and sublingual), subcutaneous, vaginal or parenteral (intramuscular, subcutaneous). And forms suitable for administration by inhalation or insufflation.

The composition of the present invention is administered in a pharmaceutically effective amount. Effective dose levels depend on the type of disease, severity, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent medications, and other factors well known in the medical field. Can be determined. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.

The dosage of the composition of the present invention varies widely depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the disease, and the appropriate dosage is, for example, Depending on the amount of drug accumulated in the body and / or the specific efficacy of the oligonucleotide used. It can be calculated on the basis of EC50, which is generally determined to be effective in in vivo animal models and in vitro, for example from 0.01 μg to 1 g per kg of body weight, in unit periods of daily, weekly, monthly or yearly It may be administered once or several times per unit period, or may be continuously administered for a long time using an infusion pump. The number of repeated doses is determined in consideration of the time the drug stays in the body, the drug concentration in the body, and the like. Even after treatment according to the course of the disease treatment, the composition can be administered for relapse.

The composition of the present invention may further contain a compound which maintains / increases the solubility and / or absorption of one or more active ingredients or the active ingredients exhibiting the same or similar functions in connection with the treatment of peripheral neurological diseases. It may also optionally further comprise chemotherapeutic agents, anti-inflammatory agents, antiviral agents and / or immunomodulators and the like.

In addition, the compositions of the present invention may be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders.

The present invention provides a dietary supplement for preventing or improving peripheral neuropathy disease comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1.

The health functional food of the present invention may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like for the purpose of preventing or improving peripheral neurological diseases.

The health functional food of the present invention refers to foods manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to Act No. 6767 of the Health Functional Food Act, and refer to nutrients for the structure and function of the human body. Ingestion is intended to obtain a beneficial effect for health use, such as regulating or physiological action.

The health functional food of the present invention may include a conventional food additive, and the suitability as a food additive is related to the item according to the General Regulations and General Test Act of the Food Additives approved by the Food and Drug Administration, unless otherwise specified. Judging by the standards and standards.

Examples of the items loaded on the food additive revolution include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid and cinnamic acid; Natural additives such as dark blue, licorice extract, crystalline cellulose, high amount of pigment and guar gum; Mixed preparations such as sodium L-glutamate, algae, preservatives, tar colorings, and the like, but are not limited thereto.

For example, a dietary supplement may be prepared by granulating a mixture of oligonucleotides consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention with excipients, binders, disintegrants and other additives in a conventional manner, and then lubricating agents. Or the like can be compression molded, or the mixture can be directly compression molded. In addition, the health functional food in the form of tablets may contain a mating agent or the like as necessary.

Hard capsules of the health functional food in the form of capsules can be prepared by filling a mixture of an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention with an additive such as an excipient in a conventional hard capsules, soft capsules of the present invention The oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 may be prepared by filling a capsule base such as gelatin with a mixture of a mixture of additives such as excipients and the like. The soft capsule agent may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.

The health functional food in a cyclic form may be prepared by molding a mixture of an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention and an excipient, a binder, a disintegrant, and the like by a conventionally known method, and if necessary, sucrose Or other coatings, or the surface may be coated with materials such as starch or talc.

The health functional food in the form of granules may be prepared by granulation of a mixture of an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention and an excipient, a binder, a disintegrant, and the like by a conventionally known method. Flavoring agents, copulating agents, and the like.

The health functional food is beverages, meat, chocolate, foods, confectionery. Pizza, ramen, other noodles, chewing gum, candy, ice cream, alcoholic beverages, vitamin complexes and dietary supplements.

Peripheral neurological disease, which is the subject of prevention or treatment of a composition comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 of the present invention, or the prevention or improvement of a dietary supplement, is acute inflammatory demyelinating polyneuropathy, chronic May be at least one selected from the group consisting of inflammatory demyelinating polyneuropathy, diabetic peripheral neuropathy, vasculitis neuropathy, hereditary peripheral neuropathy, Sharco Maritus disease, degerin sotas disease and congenital hypomyeloma Preferably it may be at least one selected from the group consisting of Sharco Maritus disease, degerin sothas disease and congenital hypomyelinated neuropathy.

Hereinafter, the present invention will be described in detail with reference to Examples.

Example  1. The present invention miRNA mRNA  At the level EGR2  Expression Inhibitory ability  analysis

After culturing the Schwann cells at a density of 2 × 10 ⁵ in a 35 mm dish, the Silenfact reagent was diluted in Opti-MEM to bind to the designated microRNA mimetics per plate, and 6 miRNAs (microRNA 152-3p, miRNA 148b). -3p, miRNA 20a-5p, miRNA 150-5p, miRNA 137-3p, miRNA) and silenfact reagent were transfected by adding them to each plate containing fresh medium and cells.

Subsequently, EGR2 mRNA expression inhibition level of each of six miRNAs (microRNA 152-3p, miRNA 148b-3p, miRNA 20a-5p, miRNA 150-5p, miRNA 137-3p, miRNA of the present invention) was measured by qRT-PCR. This is shown in FIG. 1. Referring to FIG. 1, it can be seen that only the miRNA of the present invention out of six miRNAs significantly inhibits the expression of EGR2.

Example  2. The present invention miRNA  In my vector EGR2 UTR  region expression Inhibitory ability  analysis

Using the overexpression vector for each of six miRNAs (microRNA 152-3p, miRNA 148b-3p, miRNA 20a-5p, miRNA 150-5p, miRNA 137-3p, miRNA of the present invention), Schwann cells contained a UTR region of the EGR2 gene. After transfection with the inserted plasmid, the expression inhibition level of EGR2 UTR region was measured by luciferase assay, which is shown in FIG. 2.

More specifically, Schwann cells with a pEZX-EGR2 vector having a binding site for six miRNAs (microRNA 152-3p, miRNA 148b-3p, miRNA 20a-5p, miRNA 150-5p, miRNA 137-3p, miRNA of the present invention) Was transfected with Lipofectamine 2000 (Life Technologies). Thereafter, sea pansy luciferase (Renilla luciferase) was used for standardization. Luciferase reaction was measured 48 hours later by DualLuciferase assay (Promega) using a luminometer (Promega) according to the manufacturer's instructions.

Referring to FIG. 2, it can be seen that only the miRNA of the present invention out of six miRNAs significantly inhibits the expression of the EGR2 UTR region in the vector.

Example  3. The present invention according to the postnatal development of the rat miRNA  In nerve cells Expression level  analysis

To confirm neuronal differentiation, anesthetized rats were anesthetized with a 1: 1 mixture of ketamine and lumpoon, and then the skin of the thigh was incised, and the muscle was dissected to reveal the sciatic nerve, thereby removing the exposed sciatic nerve 5 mm. 0, 1, 4, 7, 14 days after birth to obtain RNA by extracting the sciatic nerve in the adult postnatal development stage, and then measured the expression level of the miRNA of the present invention by qRT-PCR Figure 3 Shown in Referring to Figure 3 in the early stages of life maintain a high level of the expression of the present invention miRNA in neurons, the expression of the present invention miRNA in neurons steadily decreases according to postnatal development, when compared to early life when adult It can be seen that the decrease is very low.

Example  4. The present invention after peripheral nerve injury in rats miRNA  In nerve cells Expression level  analysis

Adult mouse (C57BL6) sciatic nerve axotomy was performed as known (Lee HK et al. (2007) J Neurochem 102: 686-698). All procedures were performed in accordance with the protocol approved by the Dong-A University Committee on Animal Research and in accordance with the guidelines for animal testing established by the Korean Medical Association. The sciatic nerve was cut at 5 mm away from the tibioperoneal bifurcation with sharp iris scissors (FST Inc, Foster City, Calif., USA) and regeneration was inhibited by deflecting the proximal cutting end.

After peripheral nerve injury of the rat, the RNA was obtained by extracting the sciatic nerve every 0 days, 1 day, 7 days, and 14 days, and then the expression level of the miRNA of the present invention was measured by qRT-PCR. Indicated. Referring to Figure 4, it can be seen that the expression level of the miRNA of the present invention is rapidly increased immediately after the peripheral nerve injury of the rat.

<110> Dong-A University Research Foundation for Industry-Academy Cooperation <120> Pharmaceutical composition and Health-functional food for          preventing or treating neurological disorders <130> 18P07026 <160> 8 <170> KoPatentIn 3.0 <210> 1 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> present invention miRNA <400> 1 caaagugcuu acagugcagg uag 23 <210> 2 <211> 419 <212> DNA <213> Artificial Sequence <220> <223> EGR2 region <400> 2 cctcagtacc ctggtgccag ctgctaccca gaaggcatca tcaatattgt gagtgcgggc 60 atcttgcaag gggtcacccc tccagcttca accacagcct cttccagcgt cacctctgcc 120 tcccccaacc cactggccac gggacccctg ggtgtgtgta ccatgtccca gactcagcct 180 gaactggacc acctctactc tccaccacca cctcctcctc cttattcggg ctgtacagga 240 gacctctacc aggatccttc agcattctta tcgccgccac ccaccacttc cacctcctct 300 ctggcctacc agccacctcc ttcctaccca tcccccaagc cggctatgga cccaggtctc 360 attcctatga tcccagacta tcctggattt tttccatctc cgtgccagag agatccaca 419 <210> 3 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> miRNA 152-3p <400> 3 ucagugcaug acagaacuug g 21 <210> 4 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> miRNA 148b-3p <400> 4 ucagugcauc acagaacuuu gu 22 <210> 5 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> miRNA 20a-5p <400> 5 uaaagugcuu auagugcagg uag 23 <210> 6 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> miRNA 150-5p <400> 6 ucucccaacc cuuguaccag ug 22 <210> 7 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> miRNA 137-3p <400> 7 uuauugcuua agaauacgcg uag 23 <210> 8 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> EGR2 3 'UTR region <400> 8 agcaaaacug auguggcacu uua 23

Claims (6)

A pharmaceutical composition for preventing or treating peripheral neuropathy disease comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1.
The method of claim 1, wherein the peripheral neuropathy is acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, diabetic peripheral neuropathy, vasculitis neuropathy, hereditary peripheral neuropathy, Charco Maritus disease, degerin At least one selected from the group consisting of Sotas disease and congenital hypomyelinated neuropathy.
The composition of claim 1, wherein the peripheral neurological disease is at least one selected from the group consisting of Charcoal Maritus disease, Degerin sotas disease, and congenital hypomyelinated neuropathy.
A health functional food for preventing or improving peripheral neuropathy disease comprising an oligonucleotide consisting of the nucleotide sequence of SEQ ID NO: 1.
The method of claim 4, wherein the peripheral neuropathy is acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, diabetic peripheral neuropathy, vasculitis neuropathy, hereditary peripheral neuropathy, Charco Maritus disease, degerin Health functional food which is at least one selected from the group consisting of Sotas disease and congenital hypomyeloma.
The health functional food according to claim 4, wherein the peripheral nerve disease is at least one selected from the group consisting of Charcoal Maritus disease, Degerin sotas disease, and congenital hypomyelinated neuropathy.

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