Pharmaceutical composition for preventing or treating endoplasmic reticulum stress-associated diseases

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating endoplasmic reticulum stress-associated diseases. It has been identified that a peptide having a specific amino acid sequence exhibits the effects of inhibiting endoplasmic reticulum stress, inhibiting fat synthesis, and reducing intracellular reactive oxygen species (ROS) or calcium concentration, and thus the composition can be effectively used to prevent, treat or alleviate endoplasmic reticulum stress-associated diseases.

Description

Pharmaceutical composition for preventing or treating diseases related to endoplasmic reticulum stress

[0001] The present invention relates to a pharmaceutical composition for preventing or treating diseases related to endoplasmic reticulum stress.

[0002] The endoplasmic reticulum (ER) is an organelle within eukaryotic cells that has a network-like structure made up of flat and tubular structures surrounded by membranes. It performs various functions such as protein synthesis, lipid synthesis, and transport of substances within the cell. Depending on the presence or absence of ribosomes, it is classified into the rough endoplasmic reticulum with attached ribosomes and the smooth endoplasmic reticulum without ribosomes. About one-third of the proteins in the cell become active protein structures through posttranslational modifications from mRNA to proteins in the rough ER, such as folding, assembly, glycation, and disulfide bonds. In addition, the smooth ER is a site for lipid and sterol synthesis and plays an important role in regulating intracellular calcium concentrations as a calcium storage device.

[0003] Endoplasmic reticulum (ER) stress refers to a condition in which immature proteins exceeding the ER's ability to process are introduced into the ER due to physiological or pathological circumstances, or calcium in the ER is depleted, which causes ER function to be impaired. It mainly refers to a state in which the ER protein folding load is exceeded by exceeding the protein folding capacity. When ER stress occurs, cells have a defense mechanism to survive, and this defense mechanism is mediated through the PERK (pancreatic endoplasmic reticulum kinase), IRE-1α / XBP-1 (inositol-requiring enzyme 1α / X-box binding protein 1), and ATF6 (Activating Transcription Factor 6) pathways, and this is called the ER stress response.

[0004] Diseases caused by ER stress are extremely diverse, including Parkinson's disease, glutaminase-induced aggregation disorders, Huntington's disease, Alzheimer's disease, ischemic diseases, cardiovascular diseases, neurodegenerative diseases, bipolar disorder, diabetes mellitus, atherosclerosis, inflammation, ischemia, heart diseases, liver diseases, kidney diseases, and cancer. Therefore, active research is underway to develop treatments for related diseases by modulating ER stress.

[0005] The purpose of the present invention is to provide a composition for preventing, treating or improving diseases related to endoplasmic reticulum stress.

[0006] To achieve the above purpose, the present invention provides a pharmaceutical composition for preventing or treating diseases related to endoplasmic reticulum stress, which comprises as an active ingredient a peptide or polypeptide composed of an amino acid sequence represented by the following general formula I.

[0007] Ser-Arg-X1-Thr-X2-Asp-Tyr-Leu (I)

[0008] The above X1 and X2 are one selected from the group consisting of Gly, Ala, Ser, Pro, Val, Thr, Cys, Ile, Leu, Asn, Asp, Gln, Lys, Glu, Met, His, Phe, Sec, Arg, Tyr and Trp.

[0009] In addition, the present invention provides a health functional food composition for preventing or improving diseases related to endoplasmic reticulum stress, which comprises the peptide or polypeptide as an active ingredient.

[0010] According to the present invention, it has been confirmed that a peptide having a specific amino acid sequence exhibits effects of suppressing endoplasmic reticulum stress; suppressing fat synthesis; and reducing intracellular reactive oxygen species (ROS) or calcium concentration, and thus can be usefully utilized as a composition for preventing, treating, or improving diseases related to endoplasmic reticulum stress.

[0011] Figure 1 shows the results of analyzing the effect of the STD peptide (hereinafter referred to as “sample”) prepared in Experimental Example 1 below on endoplasmic reticulum stress.

[0012] Figure 2 shows the results of analyzing the effect of the sample on fat synthesis.

[0013] Figure 3 shows the results of analyzing the binding strength of the sample and TRABID.

[0014] Figures 4 and 5 show the results of analyzing the fatty liver improvement effect of the sample using the animal model produced in Experimental Example 5 below. Specifically, Figure 4 shows the experimental results for an animal model in which the sample was intravenously injected into the tail; and Figure 5 shows the experimental results for an animal model in which the sample was subcutaneously injected.

[0015] Figure 6 shows the results of analyzing the effect of the sample on intracellular reactive oxygen species (ROS) and calcium concentration.

[0016] Figure 7 shows the results of analyzing the effect of a ring-shaped, modified sample manufactured based on a sample on fat synthesis.

[0017] Hereinafter, the present invention will be described in more detail.

[0018]

[0019] The present invention provides a pharmaceutical composition for preventing or treating diseases related to endoplasmic reticulum stress, which comprises as an active ingredient a peptide or polypeptide composed of an amino acid sequence represented by the following general formula I.

[0020] Ser-Arg-X1-Thr-X2-Asp-Tyr-Leu (I)

[0021] The above X1 and X2 may be one selected from the group consisting of Gly, Ala, Ser, Pro, Val, Thr, Cys, Ile, Leu, Asn, Asp, Gln, Lys, Glu, Met, His, Phe, Sec, Arg, Tyr and Trp.

[0022] The above peptide or polypeptide may have an amino acid sequence represented by SEQ ID NO: 1.

[0023] [Sequence number 1]

[0024] SRDTIDYL (Ser Arg Asp Thr Ile Asp Tyr Leu)

[0025] Additionally, the peptide or polypeptide may have a form represented by the following structural formula 1, structural formula 2, or structural formula 3.

[0026] [Structural formula 1]

[0027]

[0028] [Structural formula 2]

[0029]

[0030] [Structural formula 3]

[0031]

[0032] In the above structural formulas 1, 2 and 3,

[0033] Peptide1 may be a peptide or polypeptide composed of an amino acid sequence represented by the general formula I above,

[0034] Peptide2 may be a peptide or polypeptide consisting of an amino acid sequence represented by SEQ ID NO: 3.

[0035] [Sequence number 3]

[0036] RRRRRRR (Arg Arg Arg Arg Arg Arg Arg)

[0037] Additionally, the peptide or polypeptide may exhibit effects of inhibiting endoplasmic reticulum stress; inhibiting fat synthesis; or reducing intracellular reactive oxygen species (ROS) or calcium concentration.

[0038] In addition, the peptide or polypeptide may suppress the expression of one or more selected from the group consisting of PERK (protein kinase R-like endoplasmic reticulum kinase), IRE1 (inositol-requiring kinase 1), eIF2a (Eukaryotic Initiation Factor 2a), Bip (immunoglobulin binding protein), ATF4 (Activating Transcription Factor 4), CHOP (C / EBP homologous protein), ACC1 (Acetyl-CoA carboxylase 1), and DGAT2 (Diacylglycerol acyltransferase 2), but is not limited thereto.

[0039] The above endoplasmic reticulum stress-related disease may be at least one selected from the group consisting of diabetes, diabetic eye disease, obesity, glutaminase-induced aggregation disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt-Jakob disease, Wolcott-Rallison syndrome, Wolfram syndrome, ischemic disease, cardiovascular disease, neurodegenerative disease, bipolar disorder, arteriosclerosis, inflammation, ischemia, heart disease, liver disease, pancreatic disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, and cancer, but is not limited thereto.

[0040] The above liver disease may be one or more selected from the group consisting of fatty liver disease, liver fibrosis, hepatitis, and liver cancer, but is not limited thereto.

[0041] The pharmaceutical composition of the present invention can be manufactured in a unit dose form or can be manufactured by placing it in a multi-dose container by formulating it using a pharmaceutically acceptable carrier according to a method that can be easily performed by a person having ordinary skill in the art to which the present invention pertains.

[0042] The pharmaceutically acceptable carriers mentioned above are those commonly used in formulations, and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, and the like. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like.

[0043] In the present invention, the content of the additive included in the pharmaceutical composition is not particularly limited and can be appropriately adjusted within the content range used in conventional formulations.

[0044] The above pharmaceutical composition may be formulated in the form of one or more external skin preparations selected from the group consisting of injectable formulations such as aqueous solutions, suspensions, emulsions, pills, capsules, granules, tablets, creams, gels, patches, sprays, ointments, ointments, lotions, liniments, pastes, and cataplasmas, but is not limited thereto.

[0045] The pharmaceutical composition of the present invention may further comprise pharmaceutically acceptable carriers and diluents for formulation. The pharmaceutically acceptable carriers and diluents include, but are not limited to, excipients such as starch, sugar, and mannitol; fillers and extenders such as calcium phosphate; cellulose derivatives such as carboxymethylcellulose and hydroxypropylcellulose; binders such as gelatin, alginates, and polyvinyl pyrrolidone; lubricants such as talc, calcium stearate, hydrogenated castor oil, and polyethylene glycol; disintegrants such as povidone and crospovidone; and surfactants such as polysorbates, cetyl alcohol, and glycerol. The pharmaceutically acceptable carriers and diluents may be biologically and physiologically compatible with the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents, and / or dispersion media.

[0046] The pharmaceutical composition of the present invention may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method. In the case of oral administration, it may be formulated as tablets, troches, lozenges, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups, elixirs, etc. In the case of parenteral administration, it may be formulated as injections, suppositories, powders for respiratory inhalation, aerosols for sprays, ointments, powders for application, oils, creams, etc.

[0047] The dosage of the pharmaceutical composition of the present invention may vary depending on the patient's condition, weight, age, sex, health status, dietary constitution, nature of the formulation, severity of the disease, administration time of the composition, administration method, administration period or interval, excretion rate, and drug form, and may be appropriately selected by a person skilled in the art. For example, it may be in the range of about 0.1 to 10,000 mg / kg, but is not limited thereto, and may be administered once or several times a day in divided doses.

[0048] The pharmaceutical composition may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method. The pharmaceutically effective amount and effective dosage of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, administration route, etc. of the pharmaceutical composition. A person skilled in the art can easily determine and prescribe an effective dosage for the intended treatment. The pharmaceutical composition of the present invention may be administered once a day or divided into several doses.

[0049]

[0050] In addition, the present invention provides a health functional food composition for preventing or improving diseases related to endoplasmic reticulum stress, which comprises as an active ingredient a peptide or polypeptide composed of an amino acid sequence represented by the following general formula I.

[0051] Ser-Arg-X1-Thr-X2-Asp-Tyr-Leu (I)

[0052] The above X1 and X2 may be one selected from the group consisting of Gly, Ala, Ser, Pro, Val, Thr, Cys, Ile, Leu, Asn, Asp, Gln, Lys, Glu, Met, His, Phe, Sec, Arg, Tyr and Trp.

[0053] The present invention can be generally used as a commonly used food.

[0054] The food composition of the present invention can be used as a health functional food. The term "health functional food" refers to a food manufactured and processed using raw materials or ingredients with functional properties useful to the human body as defined in the Health Functional Food Act. "Functionality" refers to ingestion for the purpose of obtaining beneficial effects for health purposes, such as regulating nutrients for the structure and function of the human body or physiological effects.

[0055] The above health functional food composition may contain conventional food additives, and its suitability as the above “food additive” is determined by the specifications and standards for the relevant item in accordance with the general provisions and general test methods of the Food Additive Code approved by the Ministry of Food and Drug Safety, unless otherwise specified.

[0056] Items listed in the above “Food Additives Code” include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, high-molecular-weight pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, alkaline agents for noodles, preservative preparations, and tar color preparations.

[0057] The food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. For example, among health functional foods in capsule form, hard capsules can be manufactured by mixing and filling a composition according to the present invention with additives such as excipients into a conventional hard capsule, and soft capsules can be manufactured by mixing a composition according to the present invention with additives such as excipients and filling a capsule base such as gelatin. The soft capsules may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative, etc., as necessary.

[0058] The definitions of terms for the above excipients, binders, disintegrants, lubricants, flavoring agents, etc. are described in documents known in the art and include those with the same or similar functions. There is no particular limitation on the type of food, and all health functional foods in the conventional sense are included.

[0059] In the present invention, the term “prevention” refers to any act of inhibiting or delaying a disease related to endoplasmic reticulum stress by administering a composition according to the present invention.

[0060] In the present invention, the term “treatment” refers to any act of improving or beneficially changing the symptoms of a disease related to endoplasmic reticulum stress by administering a composition according to the present invention.

[0061] In the present invention, the term “improvement” refers to any act of improving the bad condition of a disease related to endoplasmic reticulum stress by administering a composition according to the present invention.

[0062] Hereinafter, to aid understanding of the present invention, examples will be given in detail. However, the following examples are intended only to illustrate the scope of the present invention and are not intended to limit its scope. These examples are provided to more fully explain the present invention to those of average skill in the art.

[0063]

[0064] [Experimental Example 1] Sample Preparation

[0065] The peptides (STD peptide and NC peptide) used as samples in this experiment were synthesized by Dandicure Co., Ltd. The NC peptide below was manufactured using the same method as the STD peptide and was used as a negative control for the STD peptide.

[0066] 1) STD peptide (STD; RX3D-pep-STD) (SEQ ID NO: 1: SRDTIDYL)

[0067] 2) NC peptide (NC; RX3D-pep-NC) (SEQ ID NO: 2: SADTIDYL)

[0068]

[0069] [Experimental Example 2] Cell Culture

[0070] All cell lines used in this experiment were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA). Cells were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin, and 100 μg / mL gentamicin (Thermo Fisher Scientific, Waltham, MA, USA).

[0071]

[0072] [Experimental Example 3] Western Blot Analysis

[0073] The cells cultured in the above Experimental Example 1 were washed with cold phosphate-buffered saline (PBS) and resuspended in tris-HCl (pH 7.4), 1% nonyl phenoxypolyethoxylethanol-40 (NP-40), 0.25% sodium deoxycholate (sodium deoxycholate), 150 mM NaCl, 1 mM Na3VO4 (sodium orthovanadate), and 1 mM The samples were lysed on ice using NaF-buffered radioimmunoprecipitation (RIPA) buffer. The lysates were centrifuged at 10,000 × g for 10 min at 4°C, and the supernatants were collected. Western blot analysis was performed according to the Western blotting kit manufacturer's instructions, and the proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to immobilon-P membranes. Specific proteins were then detected using the enhanced chemiluminescence Western blotting detection system.

[0074]

[0075] [Experimental Example 4] Drug Affinity Reaction Target Stability Analysis

[0076] The sample was placed in a protein isolated from the cell, reacted at room temperature for 1 hour, and treated with pronase (1 μg / ml), a protein-decomposing enzyme, over time. Then, the binding strength of the peptide and protein was confirmed through Western blot analysis (Experimental Example 3).

[0077]

[0078] [Experimental Example 5] Analysis of an animal model of acute fatty liver disease

[0079] Six-week-old C57BL / 6J male mice (purchased from Zabio Co., Ltd.) were individually housed in dedicated cages under a 12 / 12-hour light / dark cycle. Samples were injected intravenously (Example 4-1) or subcutaneously (Example 4-2) into the tail of the mice at various concentrations, and 6 hours later, tunicamycin (TM) (1.5 mg / kg) was injected intraperitoneally to induce acute fatty liver disease (n=6). Afterwards, the mice were sacrificed by administering an inhalation anesthetic (isoflurane, approximately 2 ml) (an anesthetic soaked in cotton) and their blood and liver tissues were isolated. Whole blood samples were centrifuged to separate serum and submitted for analysis. Proteins were extracted from liver tissues and subjected to Western blot analysis (Experimental Example 3) to measure protein expression.

[0080]

[0081] [Experimental Example 6] Analysis of intracellular ROS and calcium concentrations

[0082] Intracellular ROS concentration was measured using H2DCFDA fluorescent dye, a universal ROS measurement method, and intracellular calcium (Ca) was measured using Flou-4 fluorescent dye. 2 +) concentration was measured. Samples were treated with retinal epithelial cells (RPE-1 cells) for 30 minutes, and then glucose (30 mM) was additionally treated for 6 hours. Then, the cells were stained with each fluorescent dye (H2DCFDA or Flou-4) for 10 minutes. The stained cells were trypsinized, resuspended in PBS, and subjected to fluorescence analysis using a flow cytometer (FACS; Becton-Dickinson, Franklin Lakes, NJ).

[0083]

[0084] [Example 1] Analysis of the effect of suppressing endoplasmic reticulum stress

[0085] In the above Experimental Example 2, hepatocytes (AML12 cells) cultured were treated with TM (10 μg / ml) or / and the sample (2 μM), and the protein expression of ATF4 (Activating Transcription Factor 4) and CHOP (C / EBP homologous protein) was measured through Western blot analysis (Experimental Example 3), thereby analyzing the effect of the sample on endoplasmic reticulum stress.

[0086] As a result, as shown in Fig. 1, the expression of ATF4 and CHOP was significantly reduced in the sample-treated group (STD) compared to the normal group (TM and peptide-untreated group).

[0087]

[0088] [Example 2] Analysis of the effect of inhibiting fat synthesis

[0089] The sample was treated on hepatocytes (AML12 cells) cultured in Experimental Example 2 (Experimental Example 1), and the protein expression of ACC1 (Acetyl-CoA carboxylase 1) and DGAT2 (Diacylglycerol acyltransferase 2) was measured through Western blot analysis (Experimental Example 3), thereby analyzing the effect of the sample on fat synthesis.

[0090] As a result, as shown in Fig. 2, the expression of ACC1 and DGAT2 was significantly reduced in the sample-treated group (STD) compared to the normal group (peptide-untreated group).

[0091]

[0092] [Example 3] Binding analysis of samples and TRABID

[0093] TRABID, a deubiquitinating enzyme, is known to regulate protein stabilization by binding to ACC1 and DGAT2 and reducing ubiquitination. Accordingly, the binding affinity of the sample and TRABID protein was analyzed according to Experimental Example 4.

[0094] As a result, as shown in Fig. 3, after pronase treatment, TRABID expression was significantly reduced in the negative control group (NC), whereas TRABID expression was significantly increased in the sample treatment group (STD, 2 μM).

[0095]

[0096] [Example 4] Analysis of the effect of improving fatty liver

[0097] 4-1. Sample intravenous injection model

[0098] The blood concentrations of GOT (Glutamate Oxaloacetate Transaminase) and GPT (Glutamate Pyruvate Transaminase) in the blood of the animal model (animal model in which the sample was intravenously injected into the tail) produced in the above Experimental Example 5 were measured, and the expression of proteins related to endoplasmic reticulum stress and proteins related to fat synthesis were measured through Western blot analysis, thereby analyzing the effect of the sample on improving fatty liver.

[0099] As a result, as shown in Fig. 4, the blood GOT and GPT concentrations increased by TM, and the blood GOT and GPT concentrations significantly decreased in the sample treatment group (STD). In addition, in the sample treatment group, the expression of p-PERK (protein kinase R-like endoplasmic reticulum kinase), p-IRE1 (inositol-requiring kinase 1), p-eIF2a (Eukaryotic Initiation Factor 2a), Bip, ATF4, and CHOP (hereinafter referred to as endoplasmic reticulum stress-related proteins), and ACC1 and DGAT2 (hereinafter referred to as lipogenesis-related proteins) significantly decreased in a concentration-dependent manner.

[0100]

[0101] 4-2. Sample subcutaneous injection model

[0102] The effect of the sample on improving fatty liver was analyzed using the animal model (animal model in which the sample was subcutaneously injected) produced in the above experimental group 5.

[0103] As a result, as shown in Fig. 5, the blood GOT and GPT concentrations increased by TM, and the blood GOT and GPT concentrations significantly decreased in the sample treatment group (STD).

[0104]

[0105] [Example 5] Analysis of intracellular ROS and calcium concentrations

[0106] According to Experimental Example 6 above, the effect of the sample on intracellular ROS and calcium concentrations was analyzed.

[0107] As a result, as shown in Fig. 6, when glucose was treated, intracellular ROS and calcium concentrations significantly increased, and when sample (STD, 2 μM) was treated, intracellular ROS and calcium concentrations significantly decreased.

[0108]

[0109] [Example 6] Analysis of the effect of annular samples on the inhibition of lipid synthesis.

[0110] As shown in Figure 7 and below, a ring-shaped sample was prepared based on the sample. After treating hepatocytes (AML12 cells) with the ring-shaped sample, protein expression was measured through Western blot analysis (Experimental Example 3) to analyze the effect of the ring-shaped sample on fat synthesis.

[0111] 1) PTM1 (RX3D-pep-PTM1)

[0112] 2) PTM2 (RX3D-pep-PTM2)

[0113] 3) PTM3 (RX3D-pep-PTM3)

[0114] As a result, as shown in Fig. 7, among the three ring-shaped samples, PTM2 showed a decrease in the expression of ACC1, DGAT2, and Bip from a lower treatment concentration than the sample (STD peptide).

[0115]

[0116] While specific aspects of the present invention have been described in detail above, it should be apparent to those skilled in the art that these specific descriptions merely represent preferred embodiments and are not intended to limit the scope of the present invention. In other words, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for preventing or treating diseases related to endoplasmic reticulum stress, comprising as an active ingredient a peptide or polypeptide composed of an amino acid sequence represented by the following general formula I: Ser-Arg-X1-Thr-X2-Asp-Tyr-Leu (I) The above X1 and X2 are one selected from the group consisting of Gly, Ala, Ser, Pro, Val, Thr, Cys, Ile, Leu, Asn, Asp, Gln, Lys, Glu, Met, His, Phe, Sec, Arg, Tyr and Trp.

2. A pharmaceutical composition according to claim 1, characterized in that the peptide or polypeptide has an amino acid sequence represented by sequence number 1.

3. A pharmaceutical composition according to claim 1, wherein the peptide or polypeptide has a form represented by the following structural formula 1, structural formula 2, or structural formula 3: [Structural formula 1] [Structural formula 2] [Structural formula 3] In the above structural formulas 1, 2 and 3, Peptide1 is a peptide or polypeptide composed of an amino acid sequence represented by the general formula I above, Peptide2 is a peptide or polypeptide consisting of an amino acid sequence represented by sequence number 3.

4. A pharmaceutical composition according to claim 1, characterized in that the peptide or polypeptide exhibits an effect of inhibiting endoplasmic reticulum stress; inhibiting fat synthesis; or reducing intracellular reactive oxygen species (ROS) or calcium concentration.

5. A pharmaceutical composition according to claim 1, characterized in that the peptide or polypeptide inhibits the expression of at least one selected from the group consisting of PERK (protein kinase R-like endoplasmic reticulum kinase), IRE1 (inositol-requiring kinase 1), eIF2a (Eukaryotic Initiation Factor 2a), Bip (immunoglobulin binding protein), ATF4 (Activating Transcription Factor 4), CHOP (C / EBP homologous protein), ACC1 (Acetyl-CoA carboxylase 1), and DGAT2 (Diacylglycerol acyltransferase 2).

6. A pharmaceutical composition according to claim 1, wherein the endoplasmic reticulum stress-related disease is at least one selected from the group consisting of diabetes, diabetic eye disease, obesity, glutamine multimer-induced aggregation disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt-Jakob disease, Wolcott-Rallison syndrome, Wolfram syndrome, ischemic disease, cardiovascular disease, neurodegenerative disease, bipolar disorder, arteriosclerosis, inflammation, ischemia, heart disease, liver disease, pancreatic disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, and cancer.

7. A pharmaceutical composition according to claim 6, characterized in that the liver disease is at least one selected from the group consisting of fatty liver disease, liver fibrosis, hepatitis, and liver cancer.

8. A health functional food composition for preventing or improving diseases related to endoplasmic reticulum stress, comprising the peptide or polypeptide of paragraph 1 as an active ingredient.

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