CN108042790B - Application of pentapeptide KLPGF in inhibiting AChE activity - Google Patents
Application of pentapeptide KLPGF in inhibiting AChE activity Download PDFInfo
- Publication number
- CN108042790B CN108042790B CN201711431034.6A CN201711431034A CN108042790B CN 108042790 B CN108042790 B CN 108042790B CN 201711431034 A CN201711431034 A CN 201711431034A CN 108042790 B CN108042790 B CN 108042790B
- Authority
- CN
- China
- Prior art keywords
- ache
- klpgf
- peptide
- pentapeptide
- senile dementia
- 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.)
- Expired - Fee Related
Links
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 16
- 102100033639 Acetylcholinesterase Human genes 0.000 title abstract description 31
- 108010022752 Acetylcholinesterase Proteins 0.000 title abstract description 31
- 230000000694 effects Effects 0.000 title abstract description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 27
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 17
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 3
- 238000009098 adjuvant therapy Methods 0.000 claims 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 abstract description 8
- 229960004373 acetylcholine Drugs 0.000 abstract description 8
- 235000013305 food Nutrition 0.000 abstract description 4
- 210000004556 brain Anatomy 0.000 abstract description 3
- 231100000956 nontoxicity Toxicity 0.000 abstract description 3
- 125000003275 alpha amino acid group Chemical group 0.000 abstract description 2
- 239000002858 neurotransmitter agent Substances 0.000 abstract description 2
- 229940022698 acetylcholinesterase Drugs 0.000 description 25
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 7
- 108010053652 Butyrylcholinesterase Proteins 0.000 description 7
- 102100032404 Cholinesterase Human genes 0.000 description 7
- 102000002322 Egg Proteins Human genes 0.000 description 7
- 108010000912 Egg Proteins Proteins 0.000 description 7
- 235000014103 egg white Nutrition 0.000 description 7
- 210000000969 egg white Anatomy 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 6
- YRIBGSCJIMXMPJ-UHFFFAOYSA-N butyrylcholine Chemical compound CCCC(=O)OCC[N+](C)(C)C YRIBGSCJIMXMPJ-UHFFFAOYSA-N 0.000 description 5
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 3
- 238000003032 molecular docking Methods 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- QYNZLUZQWOCGCH-UHFFFAOYSA-M 2-butanoylsulfanylethyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCC(=O)SCC[N+](C)(C)C QYNZLUZQWOCGCH-UHFFFAOYSA-M 0.000 description 1
- 229940124596 AChE inhibitor Drugs 0.000 description 1
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- -1 iodothioacetyl choline Chemical compound 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses an application of pentapeptide KLPGF active peptide in inhibiting AChE activity, wherein the amino acid sequence of the AChE inhibiting peptide is Lys-Leu-Pro-Gly-Phe (KLPGF); the KLPGF active peptide can effectively inhibit AChE activity, improve the level of neurotransmitter acetylcholine in brain and achieve the effect of resisting senile dementia; the AChE inhibitory peptide has the advantages of simple structure, safety, no toxicity and strong AChE inhibitory property, and can be used for developing health-care food or medicine for assisting in relieving and treating senile dementia.
Description
Technical Field
The invention belongs to the technical field of food processing, and particularly relates to an application of pentapeptide KLPGF in inhibition of AChE activity.
Background
Alzheimer's Disease (AD), also known as senile dementia, is a common neurodegenerative disease in the elderly, manifested clinically as behavioral decline and loss of cognitive ability, such as difficulty in memory and language, behavioral disorders and mood disorders. According to the report of the world health organization, about 990 million new cases of dementia occur every year. It is expected that the population of dementia patients will approach 7500 million by 2030 and even double to 1.32 million by 2050. Therefore, senile dementia has become a major health problem affecting the elderly population worldwide.
The pathogenesis of senile dementia is very complex and is the result of multi-factor interaction. Data have shown that the formation of senile dementia is associated with inflammation, oxidation, loss of cholinergic transmission and the presence of neurofibrillary tangles. The accepted pathology of senile dementia includes the theory of cholinergic depletion and the amyloid cascade. Currently, the deletion of the brain neurotransmitter acetylcholine (ACh) is considered a key step in the pathogenesis of alzheimer's disease.
At present, AChE inhibitors such as tacrine, galantamine and huperzine A are mainly used for treating the Alzheimer disease. These chemically synthesized inhibitors can slow down the progression of the disease, but cause some adverse effects. Meanwhile, in view of the complex pathogenesis of the senile dementia and incomplete elucidation of the etiology mechanism, the search for a multi-target molecule with high efficiency, low toxicity and no side effect is one of the main trends of the current research. The food-derived active peptide has the advantages of wide source, simple preparation process, mild property, no side effect and the like, and simultaneously has various physiological activities, thereby gaining wide attention. The research and development of safe and efficient anti-senile dementia active peptide are particularly important.
Disclosure of Invention
The invention aims to provide an active peptide from egg white, which has AChE inhibitory activity, can play a role in resisting senile dementia and can be applied to the research and development of health-care foods or medicines.
The pentapeptide with the AChE inhibitory activity has the amino acid sequence of Lys-Leu-Pro-Gly-Phe (KLPGF), the molecular weight of the pentapeptide is 560.69Da, and the AChE inhibitory rate is 61.23% when the concentration is 50 mu g/mL.
The AChE inhibitory active peptide sequence comprises the core AChE inhibitory active peptide sequence, and any corresponding adjustment or modification is carried out on the core AChE inhibitory active peptide sequence.
In order to achieve the purpose, the invention is realized by the following technical scheme:
the invention uses spectrophotometry to test the inhibition activity of in vitro AChE and BChE of egg white peptide, uses acetylcholine (ACh) and butyrylcholine (BCh) as substrates respectively, mixes sodium phosphate buffer solution (pH8.0), test sample solution and AChE/BChE solution and incubates at room temperature. DTNB and ACh/BCh were then added to the mixture. The absorbance values of each set were measured (20min) at 412nm using a microplate reader. Further based on the molecular docking technology, AChE (1EVE) is used as a receptor, egg white peptide is used as a ligand to perform CDOCKER calculation, the inhibition mechanism of the CDOCKER is further explained and verified, and the toxicity of the egg white peptide is predicted through ToxinPred.
The invention has the beneficial effects that:
the AChE inhibitory active peptide is obtained by screening egg white, and the sequence of the AChE inhibitory active peptide is KLPGF. The peptide KLPGF can effectively inhibit the activity of AChE and has the potential function of improving the dynamic balance of choline in a cholinergic system of a brain, thereby improving nerve conduction and enhancing memory. Therefore, the peptide KLPGF has potential medical value and can be used for developing health products for preventing and assisting in treating degenerative nervous system diseases such as senile dementia and the like.
Drawings
Figure 1 of the invention
Fig. 1 is a perspective view of KLPGF interfacing with AChE.
Detailed Description
The following describes the embodiments of the present invention in further detail with reference to specific examples.
Materials and instruments used in the examples
5, 5' -dithiobis (2-nitrobenzoic acid) (DTNB), dimethyl sulfoxide (DMSO), iodothioacetyl choline (ACh), S-butyrylthiocholine chloride (BCh), acetylcholinesterase (AChE) from electroeel, butyrylcholinesterase (BChE) from horse serum, Sigma, USA; other reagents are all domestic analytical purifiers without special indication.
Example 1 determination of egg white active peptides in vitro AChE, BChE inhibitory Activity
mu.L of sodium phosphate buffer (pH8.0), 20. mu.L of test sample solution (50. mu.g/mL) and 20. mu.L of LAChE/BChE solution were mixed and incubated for 15 minutes at room temperature. Then 10. mu.L DTNB and 10. mu.L ACh/BCh were added to the mixture. The absorbance values of each set were measured (20min) at 412nm using a microplate reader.
Inhibition%
Wherein Abs represents the absorbance.
The result shows that the peptide KLPGF has better anti-senile dementia activity. When the concentration is 50 mu g/mL, the inhibition rate on AChE is 61.23%, and the inhibition rate on BChE is 3.29%.
Example 2 molecular docking
The crystal structure of AChE (1EVE) was obtained from PDB database, which was set as receptor protein by DS with active center position (2.855796, 64.576950, 67.98141). And (3) docking the peptide sequence with the highest activity in the step 1 with AChE by CDOCKER, and setting the parameters as follows: top Hit 10, Pose Cluster Radius 0.1.
The results indicate that the peptide KLPGF binds tightly to AChE and that the interaction between KLPGF and AChE involves amino acid residues Tyr70-Trp84-Gly118-Gly119-Trp279-Asp285-Ser286-Ile287-Phe330-Phe331-Tyr334-His440-Gly 441. Has stronger interaction with the catalytic sites of AChE (Tyr70, Trp84, Gly118, Gly119, Trp279, Tyr334 and His 440). The results of the interaction of the peptide KLPGF with AChE are shown in FIG. 1.
Example 3 toxicity prediction
The potential toxicity of the peptide was predicted by ToxinPred, with SVM scores < 0 indicating no toxicity. The results are shown in Table 1, and show that the peptide KLPGF has SVM fraction less than 0 and no toxicity.
TABLE 1 egg white peptide toxicity prediction
Based on the above full understanding of the present invention, the applicant believes that it should be easily understood by those skilled in the art that the peptides of the present invention and their related derivatives are intended to fall within the scope of the present invention.
Claims (1)
1. An application of AChE inhibitory active peptide KLPGF in preparing a medicine for the adjuvant treatment of senile dementia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711431034.6A CN108042790B (en) | 2017-12-20 | 2017-12-20 | Application of pentapeptide KLPGF in inhibiting AChE activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711431034.6A CN108042790B (en) | 2017-12-20 | 2017-12-20 | Application of pentapeptide KLPGF in inhibiting AChE activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108042790A CN108042790A (en) | 2018-05-18 |
| CN108042790B true CN108042790B (en) | 2021-01-15 |
Family
ID=62131925
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711431034.6A Expired - Fee Related CN108042790B (en) | 2017-12-20 | 2017-12-20 | Application of pentapeptide KLPGF in inhibiting AChE activity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108042790B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678928A (en) * | 2018-12-27 | 2019-04-26 | 渤海大学 | A kind of tripeptides with 1 inhibitory activity of cholinesterase and beta amyloid precursor protein cleavage enzyme |
| CN112940075B (en) * | 2021-01-07 | 2023-03-31 | 渤海大学 | Acetylcholine esterase inhibitory peptide and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104497105A (en) * | 2014-11-20 | 2015-04-08 | 渤海大学 | Pentapeptide KLPGF with auxiliary hyperglycemic function |
-
2017
- 2017-12-20 CN CN201711431034.6A patent/CN108042790B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104497105A (en) * | 2014-11-20 | 2015-04-08 | 渤海大学 | Pentapeptide KLPGF with auxiliary hyperglycemic function |
Non-Patent Citations (1)
| Title |
|---|
| Anti-diabetic activity peptides from albumin against a-glucosidase and a-amylase;Zhipeng Yu等;《Food Chemistry》;20120701;第135卷(第3期);摘要 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108042790A (en) | 2018-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Penke et al. | Oligomerization and conformational change turn monomeric β-amyloid and tau proteins toxic: Their role in Alzheimer’s pathogenesis | |
| Needleman | Lead poisoning | |
| Aldaz et al. | WWOX loss of function in neurodevelopmental and neurodegenerative disorders | |
| Celestino-Soper et al. | Deletions in chromosome 6p22. 3-p24. 3, including ATXN1, are associated with developmental delay and autism spectrum disorders | |
| Motataianu et al. | Oxidative stress in amyotrophic lateral sclerosis: synergy of genetic and environmental factors | |
| Hepp Rehfeldt et al. | c-Jun N-terminal kinase inhibitors as potential leads for new therapeutics for Alzheimer’s diseases | |
| Ziabska et al. | Aberrant complement system activation in neurological disorders | |
| Kurkinen et al. | The amyloid cascade hypothesis in Alzheimer’s disease: should we change our thinking? | |
| Tisato et al. | Genetics and epigenetics of one-carbon metabolism pathway in autism spectrum disorder: a sex-specific brain epigenome? | |
| CN108042790B (en) | Application of pentapeptide KLPGF in inhibiting AChE activity | |
| US20090117216A9 (en) | Composition and use of phyto-percolate for treatment of disease | |
| Davidson et al. | The initial common pathway of inflammation, disease, and sudden death | |
| Chen et al. | Administration of Repetitive Transcranial Magnetic Stimulation Attenuates Aβ1-42‐Induced Alzheimer’s Disease in Mice by Activating β‐Catenin Signaling | |
| Fernández-Albarral et al. | The role of autophagy in eye diseases | |
| Jarero-Basulto et al. | Current evidence on the protective effects of recombinant human erythropoietin and its molecular variants against pathological hallmarks of Alzheimer’s disease | |
| Cheng et al. | d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia | |
| Chowdhury et al. | Diverse roles of ceramide in the progression and pathogenesis of Alzheimer’s disease | |
| CA2631773A1 (en) | Composition and use of phyto-percolate for treatment of disease | |
| Salis et al. | Olive oil polyphenols in neurodegenerative pathologies | |
| Lundt et al. | NAD+ metabolism and diseases with motor dysfunction | |
| Benhamú et al. | New trends in aging drug discovery | |
| Li et al. | Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1 β-Induced Endothelium Injury | |
| Cho et al. | Reductions in hydrogen sulfide and changes in mitochondrial quality control proteins are evident in the early phases of the corneally kindled mouse model of epilepsy | |
| Wu et al. | 2-PMAP ameliorates cerebral vasospasm and brain injury after subarachnoid hemorrhage by regulating neuro-inflammation in rats | |
| Siano et al. | Molecular design and synthesis of novel peptides from amphibians skin acting as inhibitors of cholinesterase enzymes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210115 Termination date: 20211220 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |