CN105949304B - A kind of oligopeptides and its application for mitigating the cytotoxicity of specific autoantibody mediation - Google Patents
A kind of oligopeptides and its application for mitigating the cytotoxicity of specific autoantibody mediation Download PDFInfo
- Publication number
- CN105949304B CN105949304B CN201610504345.XA CN201610504345A CN105949304B CN 105949304 B CN105949304 B CN 105949304B CN 201610504345 A CN201610504345 A CN 201610504345A CN 105949304 B CN105949304 B CN 105949304B
- Authority
- CN
- China
- Prior art keywords
- oligopeptides
- cytotoxicity
- mitigating
- autoantibody
- aqp4
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses it is a kind of for mitigate specific autoantibody mediation cytotoxicity oligopeptides and its application, the oligopeptides for mitigating the cytotoxicity of specific autoantibody mediation is named as LoopC oligopeptides, the amino acid sequence of the LoopC oligopeptides from N-terminal to C-terminal successively are as follows: CVTPPSVVGGLGVTTVHGNLTAG；The application of the oligopeptides in preparation diagnosing and treating neuromyelitis optica pedigree disease medicament and device for mitigating the cytotoxicity of specific autoantibody mediation.The oligopeptides is that the amino acid sequence of foundation human body aquaporin AQP4 cell membrane exoantigen determinant designs, and zoopery confirms, which can effectively mitigate the disease symptoms of neuromyelitis optica pedigree disease in neuromyelitis optica pedigree disease model.The present invention can be combined specifically with the AQP4 autoantibody in neuromyelitis optica pedigree Disease body fluid, the ability for making it lose attack central nervous system astroglia, to play the role of mitigating the cytotoxicity of AQP4 autoantibody.
Description
Technical field
It is specifically a kind of for mitigating the cytotoxicity of specific autoantibody mediation the present invention relates to oligopeptides and its application
Oligopeptides and its application.
Background technique
Neuromyelitis optica pedigree disease (NMOSDs) is a kind of serious nervous system degenerative disease, in East Asia Region
Disease incidence is much higher than America and Europe.Itself resisting for aquaporin 4 (AQP4) is able to detect that in most NMOSD blood samples of patients
Body, this has become the important symbol object for diagnosing the disease.Although AQP4 autoantibody Producing reason is unclear, it is caused
Interpretation of the cause, onset and process of an illness system has but been illustrated substantially: the autoantibody passes through the astroglia of attack central nervous system after blood-brain barrier,
Lead to astrocyte apoptosis by the cytotoxic effect of specificity, then causes central nervous system that demyelinating disease occurs
Become.AQP4 autoantibodies are classified as one of them in the diagnostic criteria of NMOSDs2015.Clinically, usually
The lower patient of AQP4 autoantibody concentrations can obtain preferable therapeutic effect.It can be seen that the cytotoxicity of AQP4 autoantibody with
The generation and development of disease have close relationship.The cytotoxicity for mitigating AQP4 autoantibody will become having for treatment NMOSD
Efficacious prescriptions method.The effective concentration of AQP4 autoantibody is clinically reduced frequently with the method for plasma exchange at present, but this method exists
While reducing AQP4 autoantibody concentrations, the concentration of other treatment drug is also reduced, and this method cannot be guaranteed percentage
Hundred effectively.
Mainly there are large dosage of Glucocorticoid impact, plasma exchange and vein for the treatment method of NMOSD patients during acute stage at present
Inject High-dose Immunoglobulin.High dose glucocorticoid impacts the immune function that can inhibit body, to reduce AQP4 certainly
The generation of body antibody, but be used for a long time and reduce itself immunity, can induce infection or aggravate infection, cause metabolism and
Water and salt metabolic disturbance, the hyperfunction syndrome of class adrenal cortex function occurs, as edema, Diagnostic value, hypertension, glycosuria, skin become
The symptoms such as thin, moon shaped face, buffalo hump, central obesity, crinosity, acne, myasthenia and amyotrophia.Plasma exchange can be by setting
Change-blood is clear, reduces the level of the intraserous AQP4 autoantibody of the Acute Stage, but due to displacement during it is also corresponding clear
In addition to therapeutic agent every other in serum and some beneficial cell factors, chemotactic factor (CF) etc., therefore reducing AQP4 itself
The effect of other treatment means is also reduced while antibody.Injection High-dose Immunoglobulin still lacks enough cards at present
According to the validity for supporting its treatment.
Summary of the invention
The purpose of the present invention is to provide a kind of protection animal central nervous systems, reduce cytotoxicity for mitigating spy
The oligopeptides for the cytotoxicity that anisotropic autoantibody mediates and its application, to solve the problems mentioned in the above background technology.
To achieve the above object, the invention provides the following technical scheme:
It is a kind of for mitigating the oligopeptides of the cytotoxicity of specific autoantibody mediation, the amino acid sequence of the oligopeptides from
N-terminal to C-terminal successively are as follows: CVTPPSVVGGLGVTTVHGNLTAG.The oligopeptides is named as LoopC oligopeptides.
As further scheme of the invention: described for mitigating the widow of the cytotoxicity of specific autoantibody mediation
Application of the peptide in preparation diagnosing and treating neuromyelitis optica pedigree disease medicament and device.
Compared with prior art, the beneficial effects of the present invention are:
The present invention can be combined specifically with the AQP4 autoantibody in neuromyelitis optica pedigree Disease body fluid,
The ability for making it lose attack central nervous system astroglia, to play the cytotoxicity for mitigating AQP4 autoantibody
Effect.
Detailed description of the invention
Fig. 1 is the motor function scores curve synoptic diagram using the rat for making animal model after the present invention.
Fig. 2 is using the result schematic diagram for carrying out immunofluorescence experiment after the present invention to modeling animal spinal cord.
Fig. 3 is using the result schematic diagram for carrying out immunofluorescence experiment after the present invention to modeling animal spinal cord.
Fig. 4 is using the result schematic diagram for carrying out immunofluorescence experiment after the present invention to modeling animal spinal cord.
Specific embodiment
The technical solution of the patent is explained in further detail With reference to embodiment.
It is a kind of for mitigating the oligopeptides of the cytotoxicity of specific autoantibody mediation, the amino acid sequence of the oligopeptides from
N-terminal to C-terminal successively are as follows: CVTPPSVVGGLGVTTVHGNLTAG.The cell toxicant mediated for mitigating specific autoantibody
Property oligopeptides preparation diagnosing and treating neuromyelitis optica pedigree disease medicament and device in application.
The design considerations of the amino acid sequence is a cyclic structure that aquaporin AQP4 is located at outside cell membrane, by
It is located at outside cell membrane in the cyclic structure, therefore readily becomes the attack target spot of its own antibody.
Pipe operation is set to Lewis rats underwent myelin, then to rat intrathecal injection neuromyelitis optica pedigree Disease
Serum and complement, pass through in patients serum cause a disease AQP4 autoantibody and complement joint play antibody-dependant complement-mediated
Cytotoxicity, to make the rat model of neuromyelitis optica pedigree disease.By in advance by a certain amount of widow of the present invention
Incubation is handled altogether for peptide and patients serum and complement, can since the present invention is designed according to AQP4 cell membrane outer ring-like structure
Specific AQP4 autoantibody in patients serum is neutralized, its cytotoxicity is thus greatly reduced, in the base of rat animal model
The disease symptoms in behaviouristics and histology are significantly reduced on plinth.
Using in oligopeptides of the present invention and modeling again after neuromyelitis optica pedigree Disease serum, Lewis is big
It is mitigated in the symptom subordinate act of mouse, as shown in Figure 1.
The Immunofluorescence test for please referring to Fig. 2-4, in oligopeptides of the present invention and neuromyelitis optica pedigree disease
Modeling group (LoopC processing group) compares unused oligopeptides processing group of the present invention after patients serum, and the expression of AQP4 and GFAP are more,
CD45 and Ly6 are significantly reduced.GFAP is the labelled protein of astroglia, the AQP4 overwhelming majority point in central nervous system
Cloth is on the whole foot of astroglia, and CD45 and Ly6 are the marker protein of leucocyte, this shows with widow of the present invention
Peptide can neutralize pathogenic AQP4 autoantibody, the astroglia of Protection animal central nervous systems, and reduce white
Cell invades profit, mitigates the influence of inflammation.MBP is the marker protein of mature myelin, is found by comparing MBP, using the present invention
Oligopeptides processing group will also be substantially better than unused oligopeptides processing group of the present invention to the protection of spinal cord myelin.
Oligopeptides of the present invention is fixed on certain medium, by patients serum by the medium, by institute of the present invention
The oligopeptides for stating the cytotoxicity for mitigating specific antibody mediation being capable of specificity and specific AQP4 pathogenic in patients serum
Autoantibody combines, therefore the oligopeptides for securing the cytotoxicity of the present invention for being used to mitigate specific antibody mediation
Medium just has the ability for removing the autoantibody that causes a disease, therefore can play similar plasma exchange, but better than plasma exchange
The filtration of effect.
Oligopeptides of the present invention is fixed on certain medium, after Seal treatment, by the serum of patient to be detected
Be mixed with and be incubated for a period of time, then washed away by repeatedly washing the autoantibody that will be not associated in serum, only leave and
The autoantibody of oligopeptides specific binding, then the anti-human secondary antibody of the animal by having chelated certain enzyme with a certain concentration are incubated for altogether,
The pathogenic autoantibody for whether having for the oligopeptides in the patients serum is judged by the way that zymolyte progress chromogenic reaction is added.It is logical
The above method is crossed whether to diagnose in the patients serum containing the pathogenic autoantibody for the oligopeptides, realizes that specific aim is higher
Specific diagnosis facilitates formulation to have more targetedly therapeutic scheme.
Oligopeptides of the present invention is the amino acid sequence according to human body aquaporin AQP4 cell membrane exoantigen determinant
Column design, zoopery confirms, which can effectively mitigate optic nerve spinal cord in neuromyelitis optica pedigree disease model
The symptom of scorching pedigree disease, protects the myelin and astroglia of central nervous system, and reduces the infiltration of leucocyte.
The present invention can specifically in neuromyelitis optica pedigree Disease body fluid cause a disease AQP4 autoantibody
In conjunction with the ability for making it lose attack central nervous system astroglia mediates to play and mitigate AQP4 autoantibody
Cytotoxicity effect, protect central nervous system.
The preferred embodiment of the patent is described in detail above, but this patent is not limited to above-mentioned embodiment party
Formula within the knowledge of one of ordinary skill in the art can also be under the premise of not departing from this patent objective
Various changes can be made.
Claims (2)
1. a kind of for mitigating the oligopeptides of the cytotoxicity of specific autoantibody mediation, which is characterized in that the ammonia of the oligopeptides
Base acid sequence from N-terminal to C-terminal successively are as follows: CVTPPSVVGGLGVTTVHGNLTAG.
2. a kind of examine for mitigating the oligopeptides of the cytotoxicity of specific autoantibody mediation in preparation as described in claim 1
Application in disconnected and treatment neuromyelitis optica pedigree disease medicament and device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610504345.XA CN105949304B (en) | 2016-06-30 | 2016-06-30 | A kind of oligopeptides and its application for mitigating the cytotoxicity of specific autoantibody mediation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610504345.XA CN105949304B (en) | 2016-06-30 | 2016-06-30 | A kind of oligopeptides and its application for mitigating the cytotoxicity of specific autoantibody mediation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105949304A CN105949304A (en) | 2016-09-21 |
| CN105949304B true CN105949304B (en) | 2019-09-06 |
Family
ID=56902089
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610504345.XA Active CN105949304B (en) | 2016-06-30 | 2016-06-30 | A kind of oligopeptides and its application for mitigating the cytotoxicity of specific autoantibody mediation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105949304B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107643397A (en) * | 2017-07-26 | 2018-01-30 | 中国人民解放军总医院 | A kind of film bar for autoantibody parting of being caused a disease for neuromyelitis optica |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103937836A (en) * | 2014-04-04 | 2014-07-23 | 天津医科大学总医院 | Detection method of aquaporin-4 autoantibody, fusion expression virus vector and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102898513B (en) * | 2012-10-31 | 2016-03-16 | 徐俊 | ELISpot optic neuromyelitis diagnostic kit and application thereof |
-
2016
- 2016-06-30 CN CN201610504345.XA patent/CN105949304B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103937836A (en) * | 2014-04-04 | 2014-07-23 | 天津医科大学总医院 | Detection method of aquaporin-4 autoantibody, fusion expression virus vector and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105949304A (en) | 2016-09-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2949644C (en) | Composition for treating or preventing metabolic disease, containing, as active ingredient, extracellular vesicles derived from akkermansia muciniphila bacteria | |
| Tironi-Farinati et al. | Intracerebroventricular Shiga toxin 2 increases the expression of its receptor globotriaosylceramide and causes dendritic abnormalities | |
| Ren et al. | Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis | |
| JP6815413B2 (en) | Methods for Preventing and Treating Liver Tissue Injury and Related Diseases | |
| CN101790377A (en) | Prophylactic or alleviating agent for peripheral nerve disorder induced by anti-cancer agent | |
| CN110139667A (en) | A method of so that glucagon, insulin is restored normal equilibrium | |
| Hassanzadeh-Taheri et al. | Rosmarinic acid attenuates lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats | |
| CN105949304B (en) | A kind of oligopeptides and its application for mitigating the cytotoxicity of specific autoantibody mediation | |
| Smith et al. | Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis | |
| WO2010108262A1 (en) | TISSUE KALLIKREIN FOR THE TREATMENT OF PANCREATIC β-CELL DYSFUNCTION | |
| Gu et al. | Retina is protected by neuroserpin from ischemic/reperfusion-induced injury independent of tissue-type plasminogen activator | |
| CN106188268A (en) | A kind of for alleviating the Cytotoxic oligopeptide and application thereof that in blood, specific autoantibody mediates | |
| Neuschwander-Tetri | A resistance movement in NASH | |
| Zhang et al. | Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue | |
| Martins et al. | Extraintestinal manifestations of inflammatory bowel disease, nitroxidative stress and dysbiosis: What is the link between them? | |
| Kim et al. | A water-ethanol extract from the willow bracket mushroom, Phellinus igniarius (higher Basidiomycetes), reduces transient cerebral ischemia-induced neuronal death | |
| US9796760B2 (en) | Modified peptide, CB receptor ligand, kit in vitro process for evaluating CB receptor bonds, uses, pharmaceutical composition for modulating CB receptor activity | |
| JP2021517561A (en) | Compositions and Methods for Treating Neurological Disorders and Other Disorders | |
| Yang et al. | α-Synuclein pathology from the body to the brain: so many seeds so close to the central soil | |
| WO2021068432A1 (en) | Application of elapidae snake postsynaptic neurotoxin monomer molecule in treatment of alzheimer's disease | |
| CN103864930A (en) | Preparation and use method of antibody resisting scorpion venom of buthus martensii karsch in China F (ab') 2 | |
| JP2012017287A (en) | Therapeutic agent for senile disease | |
| Wu et al. | Nattokinase Promotes Post-stroke Neurogenesis and Cognition Recovery via Increasing Circulating Irisin | |
| Patchell et al. | Repair of the injury to respiratory epithelial cells characteristic of asthma is stimulated by Allomyrina dichotoma agglutinin specific serum glycoproteins | |
| JP2019520341A (en) | Compositions and methods for treating metabolic disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |