WO2017065541A1 - Composition pour la prévention ou le traitement de maladies dégénératives du cerveau - Google Patents

Composition pour la prévention ou le traitement de maladies dégénératives du cerveau Download PDF

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WO2017065541A1
WO2017065541A1 PCT/KR2016/011520 KR2016011520W WO2017065541A1 WO 2017065541 A1 WO2017065541 A1 WO 2017065541A1 KR 2016011520 W KR2016011520 W KR 2016011520W WO 2017065541 A1 WO2017065541 A1 WO 2017065541A1
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mch
melanin
degenerative brain
disease
pharmaceutical composition
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PCT/KR2016/011520
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English (en)
Korean (ko)
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전송희
김종필
박히준
Original Assignee
동국대학교 산학협력단
경희대학교 산학협력단
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Priority claimed from KR1020160132526A external-priority patent/KR20170044593A/ko
Application filed by 동국대학교 산학협력단, 경희대학교 산학협력단 filed Critical 동국대학교 산학협력단
Publication of WO2017065541A1 publication Critical patent/WO2017065541A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones

Definitions

  • the present invention relates to a pharmaceutical / health functional composition for the prevention, improvement and treatment of degenerative brain diseases, which contains melanin-concentrating hormone (MCH) as an active ingredient.
  • MCH melanin-concentrating hormone
  • degenerative brain diseases are not initially manifested by many compensatory mechanisms, they are usually diagnosed after a large number of diseases and progress slowly, irreversibly, so early detection is very important and prevents disease progression. There is an urgent need for the development of therapeutic agents to extend or prolong. In addition, for the early diagnosis and treatment of degenerative brain diseases, the development of molecular biological knowledge and the pathophysiology of degenerative brain diseases must be preceded.
  • Alzheimer's disease is characterized by senile plaques, primarily caused by the deposition of amyloid beta (A ⁇ ) peptides in brain parenchyma and cerebrovascular vessels, and by neurofibrillary tangles, mainly synapses and neurons.
  • a ⁇ amyloid beta
  • neurofibrillary tangles mainly synapses and neurons.
  • superphosphorylation of microtubule-associated protein tau accumulates in neurons, causing excessive deleterious effects on neuronal function.
  • the correlation between amyloid beta and Alzheimer's is not clear, but the focus is on the reduction of amyloid beta as a drug target for Alzheimer's.
  • AD Alzheimer's Disease
  • melanin-concentrating hormone is the first ring-shaped 19 amino acids (Asp-Phe-Asp-Met-Leu-Arg-Cys-Met-Leu-Gly-Arg-) first isolated from the pituitary gland.
  • Val-Tyr-Arg-Pro-Cys-Trp-Gln-Val is a hypothalamic peptide.
  • Dominant expression of MCH in the brain was found in the lateral hypothalamus and protrudes throughout the brain.
  • MCH is known to regulate energy homeostasis by consuming energy and stimulating feeding behavior.
  • the focus is mainly on the development of antagonists of MCH as a target for the treatment of obesity (Korean Patent Publication No. 2010-0117059).
  • MCH degenerative brain diseases such as Alzheimer's disease (AD) and dementia.
  • the present inventors have made a thorough study on the correlation between MCH and degenerative brain diseases such as Alzheimer's disease (AD) and dementia. As a result, the present inventors confirmed that the neuronal cell death induced by A ⁇ 25 -35 is reduced by MCH. Was completed.
  • AD Alzheimer's disease
  • the present invention provides a pharmaceutical composition / health functional food composition for the prevention, improvement or treatment of degenerative brain disease, containing melanin concentrating hormone (melanin concentrating hormone) as an active ingredient.
  • the present invention also provides a method for preventing, ameliorating or treating degenerative brain disease, comprising administering melanin aggregation hormone to a subject.
  • the present invention provides a melanin aggregation hormone preventive, improve or treat the degenerative brain disease.
  • the melanin aggregation hormone is characterized in that it inhibits neuronal cell death induced by amyloid beta (amyloid ⁇ ).
  • the melanin aggregation hormone is characterized by inhibiting the production of free radicals (ROS) and nitric oxide (NO) induced by amyloid beta (amyloid ⁇ ).
  • ROS free radicals
  • NO nitric oxide
  • the melanin aggregation hormone is characterized by reducing the accumulation of amyloid beta (amyloid ⁇ ).
  • the melanin aggregation hormone is characterized by increasing the expression of cAMP response element-binding protein (CREB), miogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 beta (GSK3 ⁇ ).
  • CREB cAMP response element-binding protein
  • MAPK miogen-activated protein kinases
  • GSK3 ⁇ glycogen synthase kinase 3 beta
  • the melanin aggregation hormone is characterized by increasing the expression of Brain-derived neurotrophic factor (BNDF), Tropomyosin receptor kinase B (TRKB), and postsynaptic density protein 95 (PSD-95) .
  • BNDF Brain-derived neurotrophic factor
  • TRKB Tropomyosin receptor kinase B
  • PSD-95 postsynaptic density protein 95
  • the degenerative brain disease is characterized by Alzheimer's disease or dementia.
  • the present invention also provides a method of treating degenerative brain disease, comprising administering to a subject a pharmaceutically effective amount of the pharmaceutical composition.
  • the present invention also provides a method for preventing or treating degenerative brain disease, comprising administering to a subject a pharmaceutically effective amount of the pharmaceutical composition.
  • the present invention also provides a use of the pharmaceutical composition for the treatment of degenerative brain disease.
  • the present invention provides a use of the pharmaceutical composition for preventing or treating degenerative brain disease.
  • the melanin aggregation hormone-containing composition of the present invention has little side effects and excellent therapeutic effect in degenerative brain diseases, particularly Alzheimer's disease and dementia, it is possible to provide a new treatment method over the existing therapeutic agent.
  • FIG. 4 is a view showing the results of confirming the memory enhancement effect by the treatment of melanin aggregation hormone after administration of amyloid beta 25-35.
  • Fig. 5 shows the result of confirming the reduction of accumulation of amyloid beta 1-42 by the treatment of melanin aggregation hormone in the cortex and black matter.
  • Figure 6 shows the results confirming the increase in the expression level of CREB, MAPK and GSK3 ⁇ by the treatment of melanin aggregation hormone in the cerebral cortex.
  • Figure 7 shows the results confirming the increased expression level of BNDF, TrkB, and PSD-95 by the treatment of melanin aggregation hormone in the cerebral cortex.
  • FIG. 8 is a view showing the results of confirming the increase in the expression level of CREB, MAPK and GSK3 ⁇ by the treatment of melanin aggregation hormone in the hippocampus.
  • FIG. 9 is a view showing the results confirmed the increase in the expression level of BNDF, TrkB, and PSD-95 by the treatment of melanin aggregation hormone in the hippocampus.
  • FIG. 10 is a diagram showing an experimental method (a), a Locomotor activity test result (b), and a Novel object recognition (NOR) test result (c) performed to confirm memory efficacy of melanin aggregation hormone.
  • FIG. 11 is a view showing a passive avoidance experiment results (a) and Morris water maze experiment results (b) performed to confirm the memory effect of melanin aggregation hormone.
  • the present invention provides a pharmaceutical composition / health functional food for preventing or treating degenerative brain disease, containing melanin concentrating hormone as an active ingredient.
  • 'melanin aggregation hormone' used in the present invention is a kind of neuropeptide, which is distributed in the central nervous system, and is known to be involved in dietary control and weight control of foods. It is known to have a function of softening and inhibiting melanin production.
  • the amino acid sequence of the melanin aggregation hormone is known as Asp-Phe-Asp-Met-Leu-Arg-Cys-Met-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Gln-Val ( Genbank: NP_002665, NM_002674).
  • degenerative brain disease refers to a disease in which pathological findings occur in clinical cognitive function and motor function due to early death of brain cells associated with pathological aging.
  • degenerative brain diseases include Alzheimer's disease, dementia, Huntington's disease, and the like.
  • compositions of the present invention may further comprise ingredients such as existing therapeutically active ingredients, other adjuvants, pharmaceutically acceptable carriers, and the like.
  • pharmaceutically acceptable carriers include saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and the like.
  • “individual” means a subject in need of treatment of a disease, and more specifically, human or non-human primates, mice, rats, dogs, cats, horses and cattle, etc. Mean mammal.
  • pharmaceutically effective amount means the type and severity of the disease to be administered, the age and sex of the patient, the sensitivity to the drug, the time of administration, the route of administration and the rate of administration, the duration of treatment, the elements including the drug used concurrently and other medicine It is determined according to factors well known in the art and can be easily determined by those skilled in the art in such an amount that the maximum effect can be obtained without side effects in consideration of all the above factors.
  • composition of the present invention is not limited in the "administration method" as long as the target tissue can be reached.
  • Examples include oral administration, arterial injection, intravenous injection, transdermal injection, intranasal administration, coronary administration or intramuscular administration.
  • the daily dosage is about 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg, preferably administered once to several times a day.
  • composition of the present invention can be used in a variety of drugs, foods and beverages for the prevention and improvement of degenerative brain diseases, and can be used in the form of powders, granules, tablets, capsules or beverages.
  • the present invention since there are almost no side effects and the therapeutic effect is excellent in Alzheimer's disease and dementia, it is possible to provide a new treatment method over the existing therapeutic agent.
  • Human neuroblastoma (SH-SY5Y) cells were purchased from the American Type Culture Collection (Rockville, MD, USA). Cells were 10% fetal bovine serum (FBS, Invitrogen, Carlsbad, CA, USA), 100 unit / ml penicillin, and 100 ⁇ g / ml streptoceat at 37 ° C., 95% air, and 5% CO 2 atmosphere. DMEM (Dulbeccos modified Eagles minimum essential medium, Invitrogen, Carlsbad, CA, USA) with the addition of mycin (Gibco-BRL, Rockville, MD, USA) and additionally trypsin-EDTA ).
  • FBS fetal bovine serum
  • DMEM Dulbeccos modified Eagles minimum essential medium
  • mycin Gibco-BRL, Rockville, MD, USA
  • trypsin-EDTA trypsin-EDTA
  • PCNs Primary cortical neurons extract the cerebral cortex from 17-day-old fetuses of pregnant mice and use B27 supplement, 100 unit / ml penicillin, and 100 ⁇ g / ml streptomycin (Invitrogen, Carlsbad, CA, USA) was incubated for 5 days in a medium added.
  • MTT Thiazolyl Blue Tetrazolium Bromide
  • DMSO dimethyl sulfoxide
  • Intracellular ROS production was measured using a fluorometer (Spectra Max Gemini EM, Molecular Device; Sunnyvale, CA, USA). ROS was measured by dichlorofluorescin diacetate (DCFH), a dye reagent, reacted with ROS and dichlorofluorescin (DCF). was produced and measured at 480 nm excitation and 530 nm emission wavelength.
  • DCFH dichlorofluorescin diacetate
  • DCF dichlorofluorescin diacetate
  • DCF dichlorofluorescin
  • NO was measured using a nitric oxide colorimetric assay kit (Biovision). Briefly, 85 ul of cell supernatant is mixed with nitrate reductase and reacted at room temperature for 1 hour to convert nitrate to nitrite. Thereafter, the Griess reagent is mixed and reacted at room temperature for 10 minutes. After the reaction, absorbance was measured using a microplate reader with a 540nm filter. The standard curve is used to measure the concentration of nitrite in serum.
  • the experimental animal was a healthy healthy ICR mouse purchased from Orient Bio Co., Ltd. and used for 6 weeks of age (20 ⁇ 26g) and controlled at 22 ⁇ 1 °C, 55 ⁇ 1% humidity, 12 hours light-dark cycle. In the breeding room (Dongguk University Bio Animal Testing Center), diet and drinking water were freely ingested and used for experiments after adaptive breeding for 7 days.
  • the experimental group was adapted for 1 week and then divided into 5 groups of 6 animals equally by weight, and each group was treated as follows.
  • Saline group Group that intracerebroventricular injection of saline.
  • AD group intracerebroventricular injection of ⁇ -amyloid 25-35
  • AD group + Donepezil Group administered orally at 1 mg / kg for 1 week after intracerebroventricular injection of ⁇ -amyloid 25-35.
  • AD group + MCH 1 Group administered intranasally at 1 ug / mouse for 1 week after intracerebroventricular injection of ⁇ -amyloid 25-35.
  • AD group + MCH 5 Intraprebroventricular injection of ⁇ -amyloid 25-35 for 1 week nasal administration at 5 ug / mouse.
  • a male 2-month-old (20-26 g) mouse was purchased as a transgenic mouse (APPswe / PS1dE9 Tg) imported from Orient Bio Co., Ltd.
  • the diet and drinking water were freely consumed in a 55 ⁇ 1%, 12-hour light-dark cycle, and used 4.3 months after birth.
  • mice 16 Tg-APPswe / PS1dE9 mice were divided into two groups and treated as follows.
  • MCH group (MCH) MCH 1 ug / mouse dissolved in 30 ul distilled water from 4.5 months daily (9)
  • mice were male 6-week-old (20-26 g), apparently healthy ICR mice purchased from Orient Bio.
  • the diet and drinking water were freely ingested at a controlled breeding room (Dongguk University Bio Animal Testing Center) with ⁇ 1 °C, humidity 55 ⁇ 1%, and 12 hours light-dark cycle. .
  • the experimental group was adapted for 1 week and then divided into 5 groups of 6 animals equally by weight, and each group was treated as follows.
  • Saline group Group that intracerebroventricular injection of saline.
  • MCH group 1 ug / mouse for 1 week nasal administration.
  • Scop group Group intracerebroventricular injection of scopolamine at a concentration of 1 mg / kg for 5 days.
  • Scop group + MCH Group treated with 1 g / mouse of MCH after scopolamine for 30 minutes.
  • the type of measuring device is a two-room box (shuttle box, 53cmW 44cmH ⁇ 33cmD) with a guillotine door in the middle that acts as a door between the two rooms, and one room is very suitable for creating an environment that the animals do not like. Bright bulbs are attached, while the other room is equipped with a scrambled foot-shock throughout the grid floor.
  • the test was placed in one room of each experimental group or control group, and after 15 seconds of searching time, the lighting and noise were applied through the guillotine door in the middle to reach another quiet and dark room (shock room).
  • shock room When the rat enters the shock room, the guillotine door is automatically closed and the electric shock is applied.
  • the shock was allowed to pass 0.3 mA of current for 3 seconds, and after the rat had received a foot-shock, it was taken out and placed back into the home cage. In this way, electric shock was applied to each of the seven experimental and control groups. Mice that did not enter the shock chamber for 120 seconds were excluded from the subject.
  • the step-through latency time was measured up to 300 seconds (cut-off time).
  • the water maze test was performed for 5 days.
  • a circular water tank (180 cm in diameter, 35 cm in height) was filled with water at a temperature of 22 ⁇ 2 ° C. to a depth of 15 cm and the water was crushed with milk powder.
  • the platform (4.5 cm in diameter and 13.5 cm in height) placed the entire water tank in the center of one of the quadrants so that the top of the platform was 1.5 cm below the water surface.
  • Training trials were conducted three times a day for four consecutive days. Once the mice had found the platform, they were allowed to stay on the platform for about 10 seconds and then 60 minutes later to return to the original cage. If the mouse did not find a platform within 60 seconds, it was left on the platform for 10 seconds before testing. Probe trials were conducted 24 hours after the last training trial in animals. In this case, the platform was removed from the water tank and the time spent in the quadrant where the platform was placed for 60 seconds was measured and expressed as a percentage. The experiments were recorded using a videorecorder / tracking device (S-MART; Pan-Lab, Barcelona, Spain) mounted on the ceiling above the water tank.
  • S-MART videorecorder / tracking device
  • each animal was placed in a 40 x 40 x 40 cm acrylic box for 10 minutes 30 minutes before each. After 30 minutes, the animals were placed in the center of the box and video was taken for a predetermined amount of time for 5 to 10 minutes.
  • the experiment is performed using the 40 cm x 40 cm x 40 cm acrylic box used in the OFT.
  • Two equally spaced objects were placed 10 cm from the wall (30 cm between them). The animal was placed in the middle of two objects and observed for 10 minutes. After an hour, only one of the two objects was replaced with a completely different object (the size should be similar but the texture or shape should be different). Again the animal was placed between the two objects and observed for 10 minutes. The measurements were taken from the animal's approach to the object when it was viewed with the same object and the new object's access time with the other object.
  • a ⁇ (1-40) and A ⁇ (1-42) The amount of A ⁇ in the mouse brain was measured by ELISA (human and mouse specific) method that specifically captures A ⁇ (1-40) and A ⁇ (1-42).
  • ELISA kits were purchased from Invitrogen (CA, USA). ELISA method was performed according to the method provided by invitrogen. In brief: A ⁇ (1-40) and A ⁇ (1-42) provided as standard peptides were dissolved in a given standard reconstitution buffer (55 mM sodium bicarbonate, pH 9.0) and diluted using standard dilution buffer to obtain a standard curve. Mouse brain extract was mixed to standard dilution buffer to 100 ⁇ l and placed in the prepared ELISA strip.
  • a given standard reconstitution buffer 55 mM sodium bicarbonate, pH 9.0
  • the cells were washed with 4 washing buffers, attached with detection antibodies for 1 hour, and washed again 4 times, followed by HRP conjugated secondary antibody for 30 minutes, and then washed 4 times.
  • the color reaction was stopped by adding stabilized chromogen for 30 minutes and the stop solution was added by stopping solution.
  • the degree of color reaction was measured using a spectrophotometer at 450nm wavelength. The value of each sample was compared to the standard value to calculate the absolute amount of A ⁇ contained in the sample.
  • the brain was extracted, the right brain was fixed with 4% paraformaldehyde in 0.05 M phosphate buffer (PB), and post-fixation was performed for 24 hours, followed by 24 hours in 30% sucrose.
  • Immunostaining was performed by free-floating method, using the cryomicrotome to cut the tissue to 40 mm thick and using the site containing the cerebral cortex. After floating for 10 minutes with a solution containing 3% H 2 O 2 in a 0.05 M PBS solution, the anti-Abeta1-42 (1: 100, Biosource USA) antibody was bound at room temperature for more than 16 hours, and then Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA, USA).
  • the hippocampus was isolated and buffered (50 mM Tris-HCl pH7.5, 150 mM NaCl, 2 mM EDTA, 30 mM sodium pyrophosphate, 10 mM NaF, 2 mM Na3VO4, protease inhibitor cocktail) and used a homogenizer. Homogenization. The homogenate was centrifuged at 4 ° C. for 15 minutes at 12000 rpm to obtain only supernatant. Protein quantification was performed using bicinchoninic acid (BCA, Pierce) method.
  • BCA bicinchoninic acid
  • the supernatant was added with 4X Lammlie buffer solution (62.5 mmol / 1 Tris-HCl, pH 6.8, 2% SDS, 20% glycerol, 10% 2-mercaptoethanol, and boiled at 95 ° C. % Sodium dodecylsulfate-polyacrylamide gradient gel (Invitrogen) was separated by electrophoresis (SDS-PAGE) and transferred to nitrocellulose paper (Amersham) The membrane was transferred to Ponceau-S to confirm that the protein was transferred completely.
  • Lammlie buffer solution 62.5 mmol / 1 Tris-HCl, pH 6.8, 2% SDS, 20% glycerol, 10% 2-mercaptoethanol, and boiled at 95 ° C. % Sodium dodecylsulfate-polyacrylamide gradient gel (Invitrogen) was separated by electrophoresis (SDS-PAGE) and transferred to nitrocellulose paper (Amersham) The membrane was transferred to Ponceau-S to confirm that the protein was transferred
  • TBS-T Tris-buffered saline
  • p-CREB Anti-phosphorylated CREB
  • p-MAPK anti-phosphorylated MAPK
  • MAPK MAPK
  • the membrane was reacted with anti-phosphorylated GSK3b (p-GSK3b), GSK3b, TrkB, PSD95, b-actin (Cell signaling tech. USA), and anti-BDNF antibody (Upstate Biotechnology, USA) for 16 hours at 4 ° C and then the membrane was TBS-T.
  • the blot was reacted with the secondary antibody for 1 hour After the secondary antibody reaction, the membrane was washed and enhanced chem The desired protein was visualized by an iluminiscence system (ECL, Pierce), and the image equipment (LAS-3000, Fuji) was used for visualization and quantitative analysis of the protein.
  • MTT assay was performed on human neuroblastoma cell line (SH-SY5Y) to confirm whether the neuronal cell death induced by A ⁇ 25 -35 is reduced by MCH.
  • MTT assay was performed on primary cortical neurons (PCNs) to determine whether neuronal cell death induced by A ⁇ 25 -35 is reduced by MCH.
  • MCH NO production inhibitory effect are beta of 25uM after seeding the PCN cells to identify whether a 5 days later, the cells induced by amyloid beta
  • the amount of NO produced in the cells was measured using a Nitric oxide colorimetric Assay Kit (Biovision).
  • Antagonist-MCH was used to specifically inhibit the signaling of MCH.
  • Figure 3d it was confirmed that the NO production effect induced by A ⁇ 1 -42 is reduced by 1 uM MCH.
  • Figure 3c was confirmed by immunostaining is suppressed neuronal death induced by A ⁇ 1 -42 in the MCH.
  • amyloid beta 25-35 was administered to the animal brain hippocampus using stereotaxic injection method in ICR animals as in Example 1-5-1, and then Saline, Donepezil and MCH for 10 days. And passive avoidance behavior experiments were performed one day later.
  • amyloid beta 1-42 in the cortex and black matter of the APP / PSEN transgenic animals prepared by the method of Example 1-5-2 was observed by immunostaining.
  • mice prepared by the method of 1-5-2 the effect of MCH treatment was confirmed using the immunoblot method in the cortex.
  • cAMP response element-binding protein CREB
  • mitogen-activated protein kinases MAPK
  • GSK3 ⁇ Glycogen synthase kinase 3 beta
  • cAMP response element-binding protein CREB
  • MAPK MAPK
  • GSK3b phosphorylation were all increased in the MCH group.
  • MCH increases the expression of proteins involved in neurotransmission in the cerebral cortex and hippocampus, which means that neurotransmission efficiency is increased by the treatment of MCH.
  • Locomotor activity test results are shown in Figure 10b, the scopolamine pre-treatment group to move outward compared to the normal results in the MCH treatment group.
  • Figure 10b the scopolamine pre-treatment group to move outward compared to the normal results in the MCH treatment group.
  • the time to show curiosity about the new article was increased in the MCH-treated group as shown in FIG.
  • the treatment of MCH which is an active ingredient of the composition of the present invention, can suppress neuronal cell death induced by amyloid beta and a decrease in memory, and the expression of proteins involved in neurotransmission is cortical. And both increase in the hippocampus, and confirmed through behavioral studies as a result of the memory can be seen that the MCH was confirmed that the excellent effect of the treatment of degenerative brain disease.
  • Melanin coagulation hormone-containing composition according to the present invention has little side effects and excellent therapeutic effect in degenerative brain diseases, especially Alzheimer's disease or dementia, it can provide a new method of treatment that exceeds the existing therapeutic agents, proven conventional stability Because of the use of "drug repositioning" of approved drug (MCH), there is an advantage that can reduce the risk or cost burden of new drug development.
  • MCH approved drug
  • the present invention since various signaling pathways are targeted (multi-target), a wide range of therapeutic effects can be expected, and the limitations of the single-target drug can be overcome. It can be usefully used in industry.

Abstract

La présente invention concerne une composition pharmaceutique ou une composition pour aliment fonctionnel/aliment de santé destinées à la prévention, au soulagement et au traitement de maladies dégénératives du cerveau, la composition comprenant l'hormone de mélano-concentration (MCH) comme principe actif. La composition comprenant l'hormone de mélano-concentration de la présente invention n'a quasiment pas d'effets indésirables et présente une excellente efficacité dans le traitement de maladies dégénératives du cerveau, en particulier la maladie d'Alzheimer ou la démence, et peut ainsi offrir de nouveaux traitements au-delà des médicaments existants.
PCT/KR2016/011520 2015-10-15 2016-10-14 Composition pour la prévention ou le traitement de maladies dégénératives du cerveau WO2017065541A1 (fr)

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KR10-2015-0144177 2015-10-15
KR20150144177 2015-10-15
KR10-2016-0132526 2016-10-13
KR1020160132526A KR20170044593A (ko) 2015-10-15 2016-10-13 퇴행성 뇌질환의 예방 또는 치료용 조성물

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5210076A (en) * 1988-09-13 1993-05-11 Berliner David L Methods of treating Parkinson's disease using melanin

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5210076A (en) * 1988-09-13 1993-05-11 Berliner David L Methods of treating Parkinson's disease using melanin

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
AZIZ ET AL.: "Hypocretin and Melanin-concentrating Hormone in Patients with Huntington Disease", BRAIN PATHOLOGY, vol. 18, 2008, pages 474 - 483, XP055376029 *
CARUSO ET AL.: "Synaptic Changes Induced by Melanocortin Signalling", NATURE REVIEWS NEUROSCIENCE, vol. 15, 2014, pages 98 - 110, XP055376030 *
PLATENIK ET AL.: "GSK3beta, CREB, and BDNF in Peripheral Blood of Patients with Alzheimer's Disease and Depression", PROGRESS IN NEURO-PSYCHOPHARMACOLOGY AND BIOLOGICAL PSYCHIATRY, vol. 50, 2014, pages 83 - 93, XP055376031 *
SCHMIDT ET AL.: "Cerebrospinal Fluid Melanin-concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, orexin-A) in Alzheimer's disease", PLOS ONE, vol. 8, no. 5, 2013, pages 1 - 6, XP055376027 *

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