CN106366166A - Brain-derived-neurotrophic-factor accelerant polypeptide and application - Google Patents
Brain-derived-neurotrophic-factor accelerant polypeptide and application Download PDFInfo
- Publication number
- CN106366166A CN106366166A CN201610768214.2A CN201610768214A CN106366166A CN 106366166 A CN106366166 A CN 106366166A CN 201610768214 A CN201610768214 A CN 201610768214A CN 106366166 A CN106366166 A CN 106366166A
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- group
- model
- present
- stress
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- 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)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to the field of medicine, in particular to a polypeptide capable of simulating the brain-derived-neurotrophic-factor physiological function and reducing depressive symptoms. The sequence is SEQ ID NO:1, and the SEQ ID NO:1 is a bran-new sequence. The polypeptide has the advantages that the BDNF content of chronic inscrutable stress model rat brain tissue can be increased. The in-vivo pharmacological result shows that depressive symptoms of acute and chronic depression model animals can be improved through the polypeptide, and the polypeptide can serve as an effective candidate treating method for clinical depression.
Description
Technical field
The present invention relates to Brain Derived Neurotrophic Factor accelerator polypeptide and its application are and in particular to have simulation brain source property
Neurotrophic factor physiological function, mitigates the polypeptide of depressive symptom.
Background technology
Depression (depression) be a kind of so that notable and lasting mental state is low, retardation of thinking, Cognitive function damage,
Bulesises go down and somatization is the mental sickness of main clinical characteristics, and it has high relapse rate, high disability rate and height certainly
The features such as kill risk.According to who statistics, there are 3.5 hundred million patients with depression in the whole world, and to the year two thousand twenty, depression gives people the disease that class is brought
Disease burden will be only second to ischemic heart desease, become the disabled and dead second largest reason of the mankind.
In 10 years of past, clinical in a large number and basic research makes research worker have deeper understanding to depression, grinds
Study carefully personnel be no longer regarded as depression be only in brain the low-level of 5-hydroxy tryptamine or other signaling molecules and cause.Therefore, seek
Look for the target spot of new treatment depression, develop new, effective medicament for treatment of depression, it appears particularly important.
Brain Derived Neurotrophic Factor (brain derived neurotrophic factor, bdnf) is neurotrophy
One of important member of the factor (ntfs).A kind of protein that bdnf synthesizes in intracerebral, it is distributed widely in central nervous system
Interior, during development of central nervous system, the survival of neuron, differentiation, growth promoter are played an important role, and god can be prevented
Through first damaged is dead, pathological state that is improving neuron, promote the biological effect such as damaged neuron regeneration and differentiation, and
It is also that the neuron of ripe maincenter and peripheral nervous system is survived and normal physiological function institute is required.Clinical and animal is real
Test research to show, depressed animal model usually presents the feature of low bdnf mrna level, and untreated patients with depression
Also situation that bdnf level reduce occurs.Additionally, the atrophy of patients with depression neuron and deficient phenomena are in Hippocampus and brain
Particularly evident in cortex.Experiment in vivo and vitro also shows, after long-term anti depressant therapy, bdnf in cerebral limbic system and blood plasma
Level increase, if equally antidepressant effect can be produced to depressed animal intracerebral injection bdnf, these evidences are all pointed out
Bdnf is probably the key link of anti depressant therapy.Bdnf can play and adjust painful and frightened effect.
But the molecular weight of bdnf itself is larger, has antigenicity, it is used for people for a long time and knows from experience generation neutralization reaction, reduce medicine
Effect.Therefore, the invention provides a kind of high specificity, the higher small molecule bdnf polypeptide of purity, this micromolecule polypeptide can be with mould
Intend the physiological function of bdnf, thus playing antidepressant effect.
Content of the invention
Goal of the invention
The present invention provides brand-new sequence, this sequence Brain Derived Neurotrophic Factor accelerator polypeptide, and depression is had
Curative effect well.
Technical scheme
Brain Derived Neurotrophic Factor accelerator polypeptide is it is characterised in that its sequence is seq id no:1.
Application in medicament for treatment of depression for the Brain Derived Neurotrophic Factor accelerator polypeptide.
Beneficial effect
Using solid-phase synthesis chemosynthesis Brain Derived Neurotrophic Factor accelerator polypeptide, this polypeptide has brand-new sequence
Row, this polypeptide can be used for treating depression.Molecular results show, polypeptide of the present invention can raise chronic unpredictable Stress model
Bdnf content in rat cerebral tissue.Pharmacological Results show, the polypeptide of the present invention can reduce stress be desperate in Tail suspension test
The outstanding tail time of model mice；Also can reduce in mouse forced swimming test stress desperate model mice the forced swimming time；
Meanwhile, the polypeptide of the present invention can reduce looking for food incubation period of model group rats, improves chronic unpredictable Stress model rat
In sucrose solution experiment, the picked-up to sucrose solution, compared with model group, has significant difference.As can be seen here, polypeptide of the present invention can improve
The depressive symptom of acute and chronic depression model animal.Can be used as the effective candidate therapeutics of clinical depression.
Specific embodiment
Polypeptide is by Shanghai raw work gill synthesis.
Embodiment 1
Brain Derived Neurotrophic Factor accelerator polypeptide is to bdnf in chronic unpredictable Stress model rat cerebral tissue
The impact of content.
Using sd rat as animal subject, take 60 rats, male and female half and half, body weight is 180-220g, is randomly divided into 6
Group, high dose group, middle dose group, low dose group, positive controls, model group, blank group, every group of l0 is only.Set up rat chronic
Unpredictable Stress model: stress content be: constraint 4h；Wet bedding and padding are overnight；Rock 1h (160r/min)；Fasting 12h；Frozen water is swum
4 DEG C of swimming, 10min；Rearging cage tilts 45 ° overnight；Folder tail 1min；Crowded overnight (8/cage).Daytime use two kinds stress, night
Using one kind stress, continuously stress 4 weeks.It is administered after last stimulation.Dosage regimen: the subcutaneous injection present invention is many for treatment group
Peptide, dosage is respectively 30,15,7.5mg/kg, matched group fluoxetine, dosage is 10mg/kg, and blank group gives normal saline, even
Continuous administration 7 days.1h after administration in 7th day, rat sacrificed by decapitation, go cerebral tissue, homogenate, centrifugation, take supernatant, using elisa method
(promega company) detects bdnf content.
The impact to bdnf content in chronic unpredictable Stress model rat cerebral tissue for table 1 polypeptide of the present invention
* p < 0.05, * * p < 0.01 is compared with model group
Polypeptide of the present invention is to rat chronic unpredictable Stress model result as shown in Table 1: polypeptide of the present invention can raise
Bdnf content in chronic unpredictable Stress model rat cerebral tissue, compared with model group, has significant difference.
Embodiment 2
Brain Derived Neurotrophic Factor accelerator polypeptide to mouse forced swimming test stress desperate model impact.
Using icr mice as animal subject, take 50 mices, male and female half and half, body weight is 18-22g, is randomly divided into 5 groups:
High dose group, middle dose group, low dose group, positive controls, blank group, every group of l0 is only.The subcutaneous injection present invention is many for treatment group
Peptide, dosage is respectively 30,15,7.5mg/kg, matched group fluoxetine, dosage is 10mg/kg, and blank group gives normal saline, even
Continuous administration 7 days.1h after administration in 7th day, mice carries out forced swim test, mice forced swimming 6min in 20-25 DEG C of water, note
Dead time in 4min after record, dead time, as mice stop struggling in water, the time only floating head above water,
With this evaluate polypeptide of the present invention to mouse forced swimming test stress desperate model impact.
Table 2 polypeptide of the present invention to mouse forced swimming test stress desperate model impact
| Medicine | Dosage | Number of animals (n) | Dead time (min) | |
| Blank group | —— | —— | 10 | 3.52±0.38 |
| Positive group | Fluoxetine | 10mg/kg | 10 | 1.65±0.59** |
| High dose group | Polypeptide of the present invention | 30mg/kg | 10 | 1.43±0.22** |
| Middle dose group | Polypeptide of the present invention | 15mg/kg | 10 | 1.56±0.55** |
| Low dose group | Polypeptide of the present invention | 7.5mg/kg | 10 | 1.78±0.54** |
* p < 0.05, * * p < 0.01 is compared with blank group
Polypeptide of the present invention to mouse forced swimming test stress desperate model result as shown in Table 2: polypeptide of the present invention can reduce
Forced swimming time in mice, is in dose dependent when dosage is in 7.5-30mg/kg, compared with blank group, has statistics poor
Different.
Embodiment 3
Brain Derived Neurotrophic Factor accelerator polypeptide to mouse tail suspension stress desperate model impact.
Using icr mice as animal subject, take 50 mices, male and female half and half, body weight is 18-22g, is randomly divided into 5 groups:
High dose group, middle dose group, low dose group, positive controls, blank group, every group of l0 is only.The subcutaneous injection present invention is many for treatment group
Peptide, dosage is respectively 30,15,7.5mg/kg, matched group fluoxetine, dosage is 10mg/kg, and blank group gives normal saline, even
Continuous administration 7 days.1h after administration in 7th day, mice carries out tail-suspention test, mice is fixed on its afterbody away from end about 1cm with adhesive tape
Place, makes mice keep suspension status 6min, the dead time of 4min after record, evaluating polypeptide of the present invention with this should to mouse tail suspension
Swash the impact of despair model.
Table 3 polypeptide of the present invention to mouse tail suspension stress desperate model impact
| Medicine | Dosage | Number of animals (n) | Outstanding tail time (min) | |
| Blank group | —— | —— | 10 | 3.76±0.05** |
| Positive group | Fluoxetine | 10mg/kg | 10 | 2.46±0.42** |
| High dose group | Polypeptide of the present invention | 30mg/kg | 10 | 2.46±0.47** |
| Middle dose group | Polypeptide of the present invention | 15mg/kg | 10 | 2.76±0.71** |
| Low dose group | Polypeptide of the present invention | 7.5mg/kg | 10 | 2.92±0.64** |
* p < 0.05, * * p < 0.01 is compared with blank group
Polypeptide of the present invention to mouse tail suspension stress desperate model result as shown in Table 3: polypeptide of the present invention can reduce mice
The outstanding tail time, it is in dose dependent when dosage is in 7.5-30mg/kg, compared with blank group, there is significant difference.
Embodiment 4
The impact to the unpredictable Stress model of rat chronic for the Brain Derived Neurotrophic Factor accelerator polypeptide.
Using sd rat as animal subject, take 60 rats, male and female half and half, body weight is 180-220g, is randomly divided into 6
Group, high dose group, middle dose group, low dose group, positive controls, model group, blank group, every group of l0 is only.Set up rat chronic
Unpredictable Stress model: stress content be: constraint 4h；Wet bedding and padding are overnight；Rock 1h (160r/min)；Fasting 12h；Frozen water is swum
4 DEG C of swimming, 10min；Rearging cage tilts 45 ° overnight；Folder tail 1min；Crowded overnight (8/cage).Daytime use two kinds stress, night
Using one kind stress, continuously stress 4 weeks.It is administered after last stimulation.Dosage regimen: the subcutaneous injection present invention is many for treatment group
Peptide, dosage is respectively 30,15,7.5mg/kg, matched group fluoxetine, dosage is 10mg/kg, and blank group gives normal saline, even
Continuous administration 7 days.7th day administration after 1h, rat carry out novelty look for food incubation period experiment and sucrose solution preference experiment, this is evaluated with this
The impact to the unpredictable Stress model of rat chronic for the bright polypeptide.Novelty is looked for food and is tested i.e. incubation period: laboratory animal is carrying out 24h
After fasting, animal is placed in the spacious field that a length × width × height is 76.5cm × 76.5cm × 40cm, in the middle of spacious field, is placed with one
Quantitative food, animal is put into from one jiao of spacious field, observes animal and successfully looks for food the spent time in 5min.Test simultaneously
The measurement food gross weight that consumes in 5min of animal afterwards, carrys out judgment experiment animal hunger intensity whether in this, as reference
Cause.Sucrose solution preference is tested i.e.: adapts to 48h with 1% sucrose solution by animal before sucrose solution detection, is placed in animal and is placed with after prohibiting water 4h
In the rearging cage of two identical water bottles.This two water bottles one only fill 1% sucrose solution, and another is equipped with tap water.In record 1h
Every rat drinks the volume of sucrose solution and tap water respectively.The sucrose solution volume of sucrose solution preference=drink/(the sucrose solution volume drunk+
Tap water cumulative volume) × 100%.
The impact to the unpredictable Stress model of rat chronic for table 4 polypeptide of the present invention
* p < 0.05, * * p < 0.01 is compared with model group
Polypeptide of the present invention is to rat chronic unpredictable Stress model result as shown in Table 4: polypeptide of the present invention can reduce
Looking for food incubation period of model group rats, improves the picked-up to sucrose solution in chronic unpredictable Stress model rat sucrose solution experiment, with
Model group is compared, and has significant difference.Looking for food, predominantly detect incubation period is rat anxiety-like behavior, rat sucrose solution preference table
The anhedonia tendency of clear rat.As can be seen here, polypeptide of the present invention can improve the suppression of chronic unpredictable Stress model rat
Strongly fragrant symptom.
sequence listing
<110>Suzhou Pu Luoda bio tech ltd
<120>Brain Derived Neurotrophic Factor accelerator polypeptide and its application
<130>
<160> 1
<170> patent in version 3.3
<210> 1
<211> 23
<212> prt
<213>artificial sequence
<400> 1
leu asp glu asp his lys val arg pro asn glu glu asn asn lys asp
1 5 10 15
ala asp leu tyr thr ser arg
20
Claims (2)
1. Brain Derived Neurotrophic Factor accelerator polypeptide is it is characterised in that its sequence is seq id no:1.
2. application in medicament for treatment of depression for the Brain Derived Neurotrophic Factor accelerator polypeptide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610768214.2A CN106366166A (en) | 2016-08-30 | 2016-08-30 | Brain-derived-neurotrophic-factor accelerant polypeptide and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610768214.2A CN106366166A (en) | 2016-08-30 | 2016-08-30 | Brain-derived-neurotrophic-factor accelerant polypeptide and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106366166A true CN106366166A (en) | 2017-02-01 |
Family
ID=57901763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610768214.2A Pending CN106366166A (en) | 2016-08-30 | 2016-08-30 | Brain-derived-neurotrophic-factor accelerant polypeptide and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106366166A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110664992A (en) * | 2019-11-13 | 2020-01-10 | 山东大学第二医院 | Application of BDNF in preparing medicine for treating mother-infant separation depression |
| CN111655338A (en) * | 2017-10-31 | 2020-09-11 | 免疫医疗有限公司 | Oral delivery of GLP-1 peptide analogs |
| CN111821424A (en) * | 2020-07-21 | 2020-10-27 | 广东海洋大学深圳研究院 | Application of thymosin and derivative thereof and medicament for treating depression |
| CN111840519A (en) * | 2020-08-24 | 2020-10-30 | 连庆泉 | Application of brain-derived neurotrophic factor in preparing medicine for preventing and treating propofol addiction |
| CN113181342A (en) * | 2021-05-19 | 2021-07-30 | 天津市宝恒生物科技有限公司 | Bacillus coagulans preparation for treating depression |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101921314A (en) * | 2010-06-28 | 2010-12-22 | 华中科技大学 | Brain-targeting neurotrophic factor fusion polypeptide for preventing and treating Alzheimer's disease |
| CN103102393A (en) * | 2013-01-30 | 2013-05-15 | 北京大学 | Polypeptide and application of polypeptide in preparation of drug used for treating depression |
-
2016
- 2016-08-30 CN CN201610768214.2A patent/CN106366166A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101921314A (en) * | 2010-06-28 | 2010-12-22 | 华中科技大学 | Brain-targeting neurotrophic factor fusion polypeptide for preventing and treating Alzheimer's disease |
| CN103102393A (en) * | 2013-01-30 | 2013-05-15 | 北京大学 | Polypeptide and application of polypeptide in preparation of drug used for treating depression |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111655338A (en) * | 2017-10-31 | 2020-09-11 | 免疫医疗有限公司 | Oral delivery of GLP-1 peptide analogs |
| CN110664992A (en) * | 2019-11-13 | 2020-01-10 | 山东大学第二医院 | Application of BDNF in preparing medicine for treating mother-infant separation depression |
| CN110664992B (en) * | 2019-11-13 | 2022-11-04 | 山东大学第二医院 | Application of BDNF in preparing medicine for treating mother-infant separation depression |
| CN111821424A (en) * | 2020-07-21 | 2020-10-27 | 广东海洋大学深圳研究院 | Application of thymosin and derivative thereof and medicament for treating depression |
| CN111821424B (en) * | 2020-07-21 | 2023-03-31 | 广东海洋大学深圳研究院 | Application of thymosin and derivative thereof and medicament for treating depression |
| CN111840519A (en) * | 2020-08-24 | 2020-10-30 | 连庆泉 | Application of brain-derived neurotrophic factor in preparing medicine for preventing and treating propofol addiction |
| CN111840519B (en) * | 2020-08-24 | 2023-11-28 | 连庆泉 | Application of brain-derived neurotrophic factor in preparation of drug for preventing and treating propofol addiction |
| CN113181342A (en) * | 2021-05-19 | 2021-07-30 | 天津市宝恒生物科技有限公司 | Bacillus coagulans preparation for treating depression |
| CN113181342B (en) * | 2021-05-19 | 2022-11-08 | 天津市宝恒生物科技有限公司 | Depression treating bacillus coagulans preparation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106366166A (en) | Brain-derived-neurotrophic-factor accelerant polypeptide and application | |
| McIntyre et al. | The neuroprotective effects of GLP-1: possible treatments for cognitive deficits in individuals with mood disorders | |
| Zhao et al. | Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier | |
| US9834764B2 (en) | Compositions and methods of using chondroitinase ABCI mutants | |
| CA3009034C (en) | Compositions and methods of using chondroitinase abci mutants | |
| CA2730789A1 (en) | Treatment of inflammatory bowel diseases with mammal beta defensins | |
| Lei et al. | Activation of cerebral recovery by matrix metalloproteinase-9 after intracerebral hemorrhage | |
| Liu et al. | Neurogenesis, a potential target for intermittent hypoxia leading to Cognitive decline | |
| CN101934071B (en) | Use of alpha-1-antitrypsin for the preparation of drugs for the treatment of chronic fatigue syndrome | |
| CN106349345A (en) | Glucocorticoid receptor inhibitor polypeptide and application | |
| US10160791B2 (en) | Protamine in treatment of neuronal injuries | |
| CN106366165A (en) | Sigma receptor stimulant polypeptide and application | |
| CN115595315A (en) | Novel application of ribonuclease I in pain inhibition medicine | |
| CN110420317A (en) | Application of the CBLB502 albumen in prevention and treatment posttraumatic stress disorder | |
| KR20150059671A (en) | Pharmaceutical Compositions for Preventing or Treating Parkinsonism Comprising Mesenchymal Stem Cells Derived from Human Bone-Marrow | |
| CN116139129A (en) | Application of clemastine in preparing medicine for treating depression | |
| Mojtahedzadeh et al. | Future of metformin administration in sepsis management | |
| AT511582B1 (en) | USE OF KEYHOLE-LIMPET-HEMOCYANINE OR COLD PRODUCTS THEREOF | |
| CN117180410A (en) | Medical application and pharmaceutical composition of UbV.E4B protein | |
| QIN et al. | Effects of atorvastatin on learning and memory functions in schizophrenia model rats | |
| CN106279413A (en) | D2E7 polypeptide and application | |
| RU2019128841A (en) | COMPOSITIONS AND METHODS FOR PREVENTING RADIATION DAMAGE AND STIMULATING TISSUE REGENERATION | |
| Gologorsky et al. | Let There Be Light and Muscle Contraction: Optogenetic Restoration of Muscle Function | |
| CN104000819A (en) | Treating composition for enhancing nerve regeneration of patient with cerebral infarction | |
| WO2014202833A1 (en) | Treatment of neuronal injuries |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170201 |