KR101367568B1 - Modulation of abnormal protein in neurodegenerative disease by controlling ATP-binding cassette transporter - Google Patents

Abstract

The present invention relates to a novel use of ABC transporter (ATP-binding cassette transporter) control method for preventing or treating neurodegenerative disease through the control of ATP-binding cassette transporter, a method for preventing or treating neurodegenerative disease It relates to a composition for preventing or treating a disease or degenerative neurological disease caused by abnormal ABC transporter.
The present invention can establish a new pathogenesis mechanism for neurodegenerative diseases, and there is no therapeutic drug yet, but based on the new pathogenesis mechanism, a new neurological disease treatment method, effective drug discovery, and a therapeutic agent development method and a pharmaceutical composition are provided. . The present invention is also effective in the prevention or treatment of diseases caused by ABC transporter abnormalities other than neurodegenerative diseases.

Description

Modulation of abnormal protein in neurodegenerative disease by controlling ATP-binding cassette transporter

The present invention relates to a novel use of ABC transporter (ATP-binding cassette transporter) control method for preventing or treating neurodegenerative disease through the control of ATP-binding cassette transporter, a method for preventing or treating neurodegenerative disease It relates to a composition for preventing or treating a disease or degenerative neurological disease caused by abnormal ABC transporter.

Alzheimer's disease, Parkinson's disease, Mad Cow disease (Prion disease), Huntington's disease and Amyotrophic lateral sclerosis are common etiologies of most neurodegenerative diseases such as internal and external neurons Abnormal accumulation of proteins over time and thus protein aggregation and deposition have been identified. Protein deposits formed inside and outside these cells induce hyperaccumulation and aggregation of intracellular and intracellular proteins in neurons, and toxic to cells, ultimately leading to cell death. Currently, medicines to control these symptoms have not been developed and only drugs for alleviating disease symptoms are prescribed to patients.

In order to solve the problem as described above, the present inventors studied a new use of the ABC transporter, found that by controlling the activity or expression of the ABC transporter can control the progression of degenerative neuropathy The invention has been completed.

Accordingly, an object of the present invention is to provide a method for preventing or treating neurodegenerative diseases through the regulation of ABC transporter (ATP-binding cassette transporter).

Another object of the present invention is to contact a candidate substance to differentiated neurons of Huntington's disease model mice; And it provides a method for screening a degenerative neurological disease prevention or therapeutic substance comprising the step of measuring the ABC transporter activity and the expression level of neurons in contact with the candidate substance and neurons not in contact with the candidate substance.

Another object of the present invention is to provide a substance for preventing or treating neurodegenerative diseases obtained by the screening method.

Another object of the present invention is to provide a composition for preventing or treating degenerative neurological disease, which comprises the above-mentioned degenerative neurological disease preventing or treating substance as an active ingredient.

Another object of the present invention is to provide a composition for preventing or treating a disease caused by abnormal ABC transporter containing a substance obtained by the screening method as an active ingredient.

In order to achieve the above object, the present invention provides a method for preventing or treating neurodegenerative disease through control of ABC transporter (ATP-binding cassette transporter).

In another aspect, the present invention comprises the steps of contacting the candidate substance to differentiated neurons of Huntington's disease model mice; And it provides a method for screening a substance for preventing or treating neurodegenerative diseases comprising measuring the ABC transporter activity and the expression level of neurons in contact with the candidate substance and neurons not in contact with the candidate substance.

In another aspect, the present invention provides a substance for preventing or treating neurodegenerative diseases obtained by the screening method.

In addition, the present invention provides a composition for preventing or treating degenerative neurological disease, which comprises the degenerative neurological disease preventing or treating substance as an active ingredient.

In another aspect, the present invention provides a composition for preventing or treating diseases caused by ABC transporter abnormalities containing a substance obtained by the screening method as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention provides a method for preventing or treating neurodegenerative diseases through the regulation of ABC transporter (ATP-binding cassette transporter).

The present invention is characterized by controlling the ABC transporter (ATP-binding cassette transporter).

ABC transporter (ATP-Binding Cassette transporter) is a membrane protein is a powerful substance transport protein that has a binding site to which ATP is bound and actively transports material from the intracellular cytoplasm to the cell using the ATP energy.

Substrates of these ABC transporters include estrone3-sulfate, which is an endogenous substrate, such as a number of antitumor drugs, cimetidine, toxic substances, phohpobide a, PhIP, etc. Homogeneous fluorescent dyes such as (estrone 3-sulfate), folic acid, 17-estradiol sulfate, 17-estradiol 17-(-D-glucoronide), and protopophyrin IX (PPIX) Hoechest 33342, BODIPY-prazosin, BBR 3390 and the like are known.

The ABC transporter of the present invention may be, for example, multidrug resistance protein (MDR), multidrug resistance-associated protein (MRP), mitoxantrone resistant protein (MXR), preferably MDR (multidrug resistant protein) Can be.

Degenerative neuropathy is a disease that causes various symptoms of degenerative changes in nerve cells of the central nervous system.For example, Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy. Multiple system strophy, Huntington's disease, Lou Gehrig's disease (Amyotrophic lateral sclerosis (ALS), Essential tremor, Cortico-basal ganlionic degeneration) ), Diffuse Lewy body disease, Parkin-ALS-dementia complex of Guam, Pick's disease.

Parkinson's disease is a degenerative disorder of the central nervous system that is mainly caused by degeneration of the liver and atherosclerosis. It is a major symptom of dyskinesia. It is caused by a deficiency of dopamine, a transporter.

Alzheimer's disease is the most common cause of dementia in the elderly, including histopathologic findings such as general atrophy of the brain, enlargement of the ventricles, neurofibrillary tangles and neuritic plaques. It is characterized by progressive decline of intellectual functions such as memory, judgment, language ability, and impairment of daily living ability, personality and behavior.

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a degenerative neurological disease in which the muscles under control of the cerebral and spinal cord are destroyed and muscles dominated by these cells are losing power. And clinical symptoms.

Huntington's disease is a hereditary brain disease that occurs when toxic protein aggregates form in the brain and affect the nervous system, usually beginning with facial spasms. Later, tremors spread to other parts of the body and develop into twisting movements regardless of the patient's wishes. (The chorea, meaning chorea, is synonymous with choreography, meaning dance, because the twisting movements of the chorea sometimes look a little bit like a dance.) Gradually cramping and twisting movements are used to walk, talk, and other spontaneous movements of the patient. It will further interfere with your workout. In particular, the ability to form new exercise habits declines.

Multiple sclerosis (MS) is an inflammatory and demyelinating degenerative disease of the human central nervous system (CNS). It is a disease of adolescence, with 70% -80% occurring between 20 and 40 years of age. MS is a heterogeneous disorder based on clinical course, magnetic resonance imaging (MRI) scan evaluation, and pathological analysis of biopsy and autopsy materials. This disease manifests itself in many possible combinations, including spinal cord, brainstem, cranial nerves, cerebellum, brain, and cognitive syndrome.

Meanwhile, the present invention

(a) contacting a candidate with differentiated neurons of a Huntington's disease model mouse; And (b) measuring the amount of ABC transporter activity and expression of neurons contacted with the candidate and neurons not contacted with the candidate.

Hereinafter, the method of the present invention will be described step by step.

(a) contacting candidates with differentiated neurons in Huntington's disease model mice

In step (a), candidates are contacted with differentiated neurons of Huntington's disease model mice.

Candidates are substances that are applicable to living organisms that are expected to be effective in preventing or treating neurodegenerative diseases. Candidates of the present invention include any substance, molecule, element, compound, entity, or combination thereof. For example, but not limited to, proteins, polypeptides, small organic molecules, polysaccharides, polynucleotides, and the like. It may also be a natural product, a synthetic compound or chemical compound, or a combination of two or more substances. Unless otherwise specified, the agents, substances and compounds may be used interchangeably.

Candidates that can be screened or identified by the methods of the invention include polypeptides, beta-turn mimetics, polysaccharides, phospholipids, hormones, prostaglandins, steroids, aromatic compounds, heterocyclic compounds, benzodiazepines , Oligomeric N-substituted glycines, oligocarbamates, saccharides, fatty acids, purines, pyrimidines or derivatives thereof, structural analogs or combinations thereof. Such candidates can be obtained from a wide variety of sources, including libraries of synthetic or natural compounds. Preferably, the candidate may be a peptide, such as a peptide having about 5-30, preferably about 5-20, more preferably about 7-15 amino acids. The peptide may be a cleavage of a naturally occurring protein, random peptide or “biased” random peptide.

The candidate may also be "nucleic acid." Nucleic acid candidates can be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids.

In addition, the candidate material may be a small molecule (eg, a molecule having a molecular weight of about 1,000 or less). Preferably, a high throughput assay can be applied to the method for screening a control preparation of a small molecule.

Candidates of the present invention are, for example, substances capable of promoting transcription of ABC transporter genes, substances that activate transcriptional activators known to induce transcriptional activity of ABC transporter genes, which regulate ABC transporter mRNAs. RNA species (siRNA, miRNA, iRNA), may be a substance that activates the ABC transporter protein (TWD1 / FKBP42).

(b) measuring the amount of ABC transporter activity and expression of neurons in contact with the candidate and neurons not in contact with the candidate;

In step (b), the levels of ABC transporter activity and expression of neurons in contact with the candidates and neurons without contacting the candidates are measured.

The method of measuring ABC transporter activity and expression level is hybridization test to confirm the binding between the gene and the test substance in vitro, Northern blot analysis after reacting the mammalian cells and the test substance ( northern blot assay), quantitative PCR, quantitative real-time PCR, or the like, or a method of connecting a reporter gene to the gene and introducing the cell into a cell, reacting with a test substance, and measuring a reporter protein expression rate, etc. Can be used.

Degenerative nephropathy can be prevented or treated in accordance with the regulation of the ABC transporter activity and expression of neurons, and thus can be screened for substances capable of preventing or treating degenerative neurological diseases by the above method.

Therefore, the present invention provides a substance for preventing or treating neurodegenerative diseases obtained by the screening method.

A substance for preventing or treating a neurodegenerative disease refers to a substance applicable to a living organism that is effective in preventing or treating a neurodegenerative disease. For example, a substance capable of promoting transcription of the ABC transporter gene and a transcriptional activity of the ABC transporter gene. It may be a substance that activates a transcriptional activator known to induce, RNA species that regulate ABC transporter mRNA (siRNA, miRNA, iRNA), a substance that activates ABC transporter protein (TWD1 / FKBP42). More preferably, it may be microRNA27a, and most preferably may be microRNA27a which is RNA represented by SEQ ID NO: 1.

microRNA (miRNA) refers to non-coding RNA (RNA), which assists the regulation of gene expression, particularly during development.

In one embodiment of the present invention, a variety of candidates were contacted with differentiated neurons of Huntington's disease model mice to determine whether the activity of the ABC transporter was increased. As a result, it was confirmed that the microRNA27a increases the expression of MDR1, one of the ABC transporters.

In another embodiment of the present invention, the microRNA27a represented by SEQ ID NO: 1 was subjected to Huntington's disease in vitro model to measure the change in the aggregation rate of the mutant huntingtin. As a result, in the group treated with microRNA27a, it was confirmed that the aggregation of the mutant huntingtin decreased.

As described above, the substance for treating neurodegenerative diseases of the present invention is excellent in preventing and treating neurodegenerative diseases.

Accordingly, another object of the present invention is to provide a composition for preventing or treating degenerative neurological disease, comprising the above-mentioned degenerative neurological disease preventing or treating substance as an active ingredient.

In addition, the screening method of the present invention can screen for substances that prevent or treat degenerative neurological diseases, and at the same time can screen for substances that can regulate ABC transporter activity and expression.

Therefore, the present invention provides a composition for preventing or treating a disease caused by an abnormal ABC transporter containing a substance obtained by the screening method as an active ingredient.

Degenerative neuropathy is a disease that causes various symptoms of degenerative changes in nerve cells of the central nervous system.For example, Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy. Multiple system strophy, Huntington's disease, Lou Gehrig's disease (Amyotrophic lateral sclerosis (ALS), Essential tremor, Cortico-basal ganlionic degeneration) ), Diffuse Lewy body disease, Parkin-ALS-dementia complex of Guam, Pick's disease.

Preferably, the degenerative nephropathy of the present invention may be Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease, Huntington's disease and multiple sclerosis.

ABC transporter (ATP-Binding Cassette transporter) is a membrane protein is a powerful substance transport protein that has a binding site to which ATP is bound and actively transports material from the intracellular cytoplasm to the cell using the ATP energy.

Substrates of these ABC transporters include estrone3-sulfate, which is an endogenous substrate, such as a number of antitumor drugs, cimetidine, toxic substances, phohpobide a, PhIP, etc. Homogeneous fluorescent dyes such as (estrone 3-sulfate), folic acid, 17-estradiol sulfate, 17-estradiol 17-(-D-glucoronide), and protopophyrin IX (PPIX) Hoechest 33342, BODIPY-prazosin, BBR 3390 and the like are known.

Therefore, the disease caused by the ABC transporter abnormality may be a disease involving the ABC transporter substrate, preferably may be cancer, and more specifically, may be cancer with cancer resistance.

In one embodiment of the present invention, the neural stem cell culture was performed from Huntington's disease genetically modified animal model in order to make an in vitro model of neurodegenerative disease and induced differentiation of cultured neural stem cells into various neuronal cells under differentiation conditions. As a result, the aggregation and accumulation of the mutant huntingtin, the abnormal protein of Huntington's Hospital, was confirmed in the differentiated cells. In addition, it was confirmed that the multidrug-resistant protein decreases due to aggregation and accumulation of intracellular mutant huntingtin.

In another embodiment of the present invention, the inhibition of the multidrug-resistant protein in the established Huntington's disease in vitro model was confirmed to increase the aggregation and accumulation of the mutant huntingtin.

The compositions of the present invention may be administered orally or parenterally, in either nothing or in combination with pharmaceutical carriers of the prior art. Applicable solid carriers may include one or more ingredients that may also serve as flavorings, lubricants, solubilizing agents, suspending agents, fillers, glidants, compression aids, binders, tablet disintegrating agents, or encapsulating materials, but It is not limited. In the case of powders, the carrier can be a micronized solid which can be mixed with the micronized active ingredient.

In the case of tablets, the active ingredient can be mixed with the carrier having the appropriate compression properties in suitable proportions and compacted in the shape and size desired. Powders and tablets may contain up to about 99% of the active ingredient. Suitable solid carriers are for example calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, low melting wax ), And ion exchange resins. Liquid carriers can be used to prepare solutions, suspensions, emulsions, syrups and elixirs.

In addition, for parenteral administration, the carrier may be ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. Liquid pharmaceutical compositions that are sterile solutions or suspensions can be used, for example, by intramuscular injection, intraperitoneal injection or subcutaneous injection. Sterile solutions can also be administered intravenously.

Oral administration may be in the form of a liquid or solid composition. In one embodiment, the compositions of the present invention are in unit dosage form such as, for example, tablets or capsules. In this form, the composition may be subdivided into unit doses containing appropriate amounts of the active ingredient. The unit dosage form may be a packaged composition, such as a packaged powder, vial, ampoule, prefilled syringe or sachet containing liquid.

The active ingredient of the composition of the present invention may be converted into a daily dose of about 0.01 to about 100 mg per kg of body weight per day. However, the particular dosage used may vary depending on the requirements of the patient, the severity of the disease the patient has and the activity of the compound. Determination of the optimal dosage in certain circumstances can be made clinically and is within the skill of the art.

As described above, the present invention can establish a new pathogenesis mechanism for neurodegenerative diseases, and there are no therapeutic drugs so far, but based on the new pathogenesis mechanism, a new method for treating neurological diseases, an effective drug discovery method, and a therapeutic agent development method and a pharmaceutical To provide a composition. The present invention is also effective in the prevention or treatment of diseases caused by ABC transporter abnormalities other than neurodegenerative diseases.

1 is a neurosphere culture culture (neurosphere) derived from Huntington's disease genetically modified animal model.
Figure 2 is an immunofluorescence staining showing the differentiation ability of neural stem cells derived from Huntington's disease genetically modified animal model (MAP2 &Tuj1; neuron, GFAP; astrocyte, O4; oligodendrocyte).
3 shows immunofluorescence staining using antibodies (Em48) in response to mutant huntingtin aggregation after induction of differentiation of neural stem cells derived from Huntington's disease genetically modified animal model (Blue; Dapi, Red; Em48-mutant huntingtin aggregation).
Figure 4 is a fluorescence staining (Red) of the aggregation of the mutant huntingtin protein according to the differentiation process in Huntington's disease in vitro model.
5 is a result of examining the expression of multi-drug resistant protein in Huntington's disease in vitro model, it is a diagram showing that the expression of the single-resistant protein is reduced when differentiated.
Figure 6 is a schematic diagram of the function of the multidrug-resistant protein (MDR) and mass transfer through the inhibitor.
7 is a result showing the phenomenon that the function of the multidrug-resistant protein is reduced when the cells differentiate as an efflux experiment of the multidrug-resistant protein in Huntington's disease in vitro model.
8 is a result showing that the aggregation of mutant huntingtin is increased when the multidrug-resistant protein is inhibited in the Huntington's disease in vitro model.
9 is a result showing that the aggregation of the mutant huntingtin is reduced when the microRNA27a treatment in the Huntington's disease in vitro model (round circle is the cell where the huntingtin aggregation occurred).
FIG. 10 is a graph showing the quantification of the decrease in aggregation of mutant huntingtin when treated with microRNA27a in the Huntington's disease in vitro model (Em48 / Dapi: portion stained with Em48 that specifically responds to mutant huntingtin protein aggregation). Ratio of portions stained with DAPI (4 ', 6-diamidino-2-phenylindole).

Hereinafter, one preferred embodiment of the present invention will be described in detail.

The invention can be better understood by the following examples, which are intended for the purpose of illustration of the invention and are not intended to limit the scope of protection defined by the appended claims.

Example 1: Establish Huntington's Disease In vitro Model

Trypsin / EDTA after obtaining subventricular zone (SVZ) tissue from newborn mice born in Huntington's disease animal B6CBA-Tg (HDexon1) 62Gpb / 1J (Jackson laboratory, USA) for culturing neuronal stem cells in Huntington's disease transgenic animal model Cells were isolated, cells were centrifuged at 250 g for 10 minutes to obtain cells, and then cultured in DMEM / F12 medium + B27 + 20 ng / ml bFGF + 20 ng / ml epidermal growth factor culture.

As a result, as shown in Figure 1, through the passage of Neurosphere passage to secure the number of cells to be used for Huntington's disease n vitro experiment.

In order to confirm the suitability of the cultured Huntington's disease animal model-derived neural stem cells as a model of Huntington's disease in vitro, differentiation into neurons was induced with specialized neuronal differentiation media (Stem cell corporation). After differentiation, neuronal differentiation efficiency was examined using neuronal antibodies (GFAP; astrocyte, Tuj1 and MAP2; neuron, O4; oligodendrocyte).

As a result, as shown in Figure 2, the differentiation of neurons and glia cells were confirmed, and the differentiated cells were used as an in vitro model of Huntington's disease.

Example 2: Investigation of aggregation and accumulation of mutant huntingtin in Huntington's disease in vitro model

Immunological staining for intracellular mutant huntingtin protein aggregation using Em48 (MAB5374; Milllipore) antibodies that specifically respond to mutant huntingtin protein aggregation to see mutant huntingtin protein aggregation and accumulation in established Huntington's disease in vitro models Was carried out.

As a result, as shown in Figure 3, it was confirmed that the Em48 immune response in the Huntington's disease in vitro model, which results in a condition that satisfies the observation of changes in mutant huntingtin protein aggregation in the Huntington's disease in vitro model.

Example 3: Multidrug-Resistant Protein Expression and Function Tests According to Mutant Hunting Aggregation in Huntington's Disease In vitro Model

As in Example 2, mutant huntingtin protein aggregation in neuronal stem cells / progenitor cells and differentiated neuronal cells in Huntington's disease in vitro model was investigated.

As a result, as shown in Figure 4, the mutant huntingtin protein aggregation was not observed in the neuronal stem cell / progenitor cell state, it was confirmed that the aggregation of the mutant huntingtin protein only in differentiated neuronal cells.

In addition, we examined the expression of multidrug-resistant protein in Western Huntington's disease in vitro model using western blot in neuronal stem cells / progenitor cells and differentiated neuronal cells. Proteins were extracted from neuronal stem cell / progenitor cells and neuronal cells differentiated by incubating them in differentiation conditions. The amount of multidrug-resistant protein in neuronal stem cell / progenitor cells and differentiated neuronal cells by western blot method using antibodies (MDR-snata: SantaCruz sc-8313, MDR-Abcam: Abcam ab3366) as antigens Was measured.

As a result, as shown in Figure 5, it was confirmed that the expression of the multidrug-resistant protein in the differentiated neuronal cells compared to the neuronal stem cell / progenitor cell.

In addition, the multidrug resistance (MDR) fluorescence efflux assay system in neuronal stem cells / progenitor cells and differentiated neuronal cells in Huntington's disease in vitro model was used to investigate the function of multidrug-resistant proteins.

Multidrug-resistant proteins (MDR) move the substance out of the cell and the influx of the substance into the cell is through diffusion. When the substance enters the cell, it enters by passive diffusion, and the multidrug-resistant protein acts to efflux the substance out of the cell again (Fig. 6A). Using this mechanism, the intracellular fluorescent material was added, and then the function of the multidrug-resistant protein was inhibited by the multi-drug-resistant protein inhibitor (verapamil) (Fig. 6B). The outflow amount was measured. In other words, it is a system that measures the function of multi-drug-resistant protein by measuring the flow rate of cytokines fluorescence through inhibition of multi-drug-resistant protein, and the higher the function of the multidrug-resistant protein, the less the outflow of fluorescence through the inhibitor. The difference is large (Fig. 7A).

As a result, as shown in Figure 7, it was confirmed that the function of the multidrug-resistant protein in the neuronal stem cell conditions, it was confirmed that the multi-drug-resistant protein function is reduced in differentiated neuronal cells.

Example  4: Multidrug resistance  Changes in Abnormal Protein Aggregation and Accumulation through Protein Inhibition

In the Huntington's disease in vitro model, we investigated the inhibition of intracellular multidrug-resistant protein and the aggregation and accumulation of mutant Huntingtin protein using a verapamil inhibitor.

As a result, as shown in Figure 8, it was confirmed that mutant huntingtin aggregation increased in the experimental group (Verapamil) in which the function of the multidrug-resistant protein was inhibited.

As a result of Examples 3 and 4, it was confirmed that there is a correlation between a decrease in multidrug-resistant protein expression or a decrease in function and the aggregation of mutant huntingtin protein.

Example  5: microRNA27a Of neurodegenerative diseases

Screening experiments for the treatment of neurodegenerative diseases of the present invention was carried out on a variety of candidates. Candidates were contacted with differentiated neurons in Huntington's disease model mice to determine whether ABC transporter activity was increased. As a result, it was confirmed that the microRNA27a increases the expression of MDR1, one of the ABC transporters (results not shown).

The excavated candidate microRNA27a was treated in an in vitro model of Huntington's disease to observe a change in the aggregation rate of the mutant huntingtin in the same manner as in Example 2.

As a result, as shown in [FIG. 9] and [FIG. 10], when the microRNA27a of this invention was processed, it was confirmed that aggregation of the mutant huntingtin is reduced.

As a result, the screening method of the present invention was effective in discovering a therapeutic agent for neurodegenerative diseases, and the microRNA27a of the present invention was confirmed to be effective in treating neurodegenerative diseases.

Therefore, the present invention can establish a new pathogenesis mechanism for neurodegenerative diseases, and there is no therapeutic drug yet, but based on the new pathogenesis mechanism, a new neurological disease treatment method, an effective drug discovery method, a drug development method, and a pharmaceutical composition to provide. In addition, the present invention is effective in the prevention or treatment of diseases caused by ABC transporter abnormalities other than degenerative neurological diseases, and thus has high industrial applicability.

Attach an electronic file to a sequence list

Claims (10)

delete A method for screening a substance for preventing or treating neurodegenerative diseases comprising the following steps.
a) contacting candidates with differentiated neurons of Huntington's disease model mice; And
b) measuring the amount of ABC transporter activity and expression of neurons in contact with the candidate and neurons not in contact with the candidate.
delete delete delete delete delete delete Huntington's disease prevention or treatment composition containing microRNA27a (accession No NR_029501) as an active ingredient.
The composition of claim 9, wherein the microRNA27a is RNA represented by SEQ ID NO: 1.

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