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Small peptide with nerve protection effect and application

A technology of neuroprotection and action, applied in the field of biomedicine, can solve the problems of adverse reactions of antiepileptic drugs, interference and combination, etc., and achieve the effect of improving the survival of neurons

Inactive Publication Date: 2019-03-01
XUZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to solve the problem of adverse reactions of antiepileptic drugs in the prior art. The inventors conducted in-depth research on the interaction between NETO2 and KARs, aiming to find new drug targets for the treatment of epilepsy, and finally designed a A small peptide with neuroprotective effect for interfering with the interaction of GluK2 and NETO2

Method used

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  • Small peptide with nerve protection effect and application
  • Small peptide with nerve protection effect and application
  • Small peptide with nerve protection effect and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1 Design of Small Peptides with Neuroprotective Effects

[0019] A small peptide was designed according to the highly conserved sequence of the LBD domain of the GluK2 protein and the CUB binding region (ERMESPID) of NETO2, and a small shuttle peptide (YGRKKRRQRRR) was added to its front end to allow it to enter the cell and interfere with the binding of Gluk2 and NETO2. The amino acid sequence of the small peptide with neuroprotective effect is: YGRKKRRQRRRERMESPID. Small peptides were synthesized by Shanghai Qiangyao Biotechnology Co., Ltd.

Embodiment 2

[0020] Example 2 The protective effect of small peptides on neuron damage after KA-induced epilepsy

[0021] (1) Establishment of rat epilepsy model

[0022] The epilepsy model was induced by KA (0.6 μg / 10 μl) in the lateral ventricle (the control group was given the same dose of solvent), SD rats (230-250 g) were anesthetized with isoflurane by means of an animal anesthesia machine, and fixed in a mouse brain stereotaxic instrument. The skull remains in a horizontal position. Disinfect the skin, incise the scalp to expose the skull, and wash with H 2 o 2 Caulter exposes bregma. Locate the lateral ventricle: 0.8mm posterior to the anterior bregma, 1.5mm lateral to the right, and 3.5mm downward from the surface of the skull. Drill a hole with a 1.5mm drill bit, and withdraw the cerebrospinal fluid with a microsyringe to verify the correctness of the position. The establishment standard of KA-induced epilepsy model is according to Racine classification: grade 1 is closed ey...

Embodiment 3

[0025] Example 3 Effects of small peptides on the interaction of GluK2-NETO2 after KA-induced epilepsy

[0026] (1) Sample preparation

[0027] SD male rats were randomly divided into sham operation group sham and KA administration 6h after modeling, small peptide and control peptide (sham, KA6h, Tat-GluK2+KA, Tat-scramble-GluK2+KA). Then the brain was quickly decapitated, placed in ice-cold PBS, and the CA1 and CA3 / DG regions of the hippocampus were separated, and frozen in liquid nitrogen for future use. Homogenize to extract cytoplasmic protein, and the operation is carried out in an ice bath: take out the hippocampus in liquid nitrogen, add ice-cold homogenization buffer at a ratio of 1:10 (w / v), and homogenize at a high speed with a Glas-Col homogenizer, each The time and frequency of sample homogenization were fixed, and then the supernatant was transferred with an Eppendorf-5840R desktop centrifuge at 14,000rpm, 4°C, for 30min, which was mainly cytoplasmic protein. Th...

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Abstract

The invention relates to a small peptide with a nerve protection effect, which belongs to the technical field of biological medicine. An amino acid sequence of the small peptide is YGRKKRRQRRRERMESPID. The small peptide is designed according to a highly conserved sequence of a GluK2 protein LBD structural domain and a CUB combined region of NETO2, a shuttle small peptide is added on the front end,so that the shuttle small peptide enters cells to interfere the combination of Gluek2 and NETO2, the small peptide of the invention can interfere the combination of GluK2 and NETO2, so that the nervecell survival situation caused by KA-induced epilepsy can be apparently improved, a drug adopting the small peptide as an active ingredient can be used as the epilepsy resisting drug and can be usedfor treating the epilepsy, thereby having important significance for providing a novel drug action target for the treatment of the epilepsy diseases, and solving the problems in the prior art that theepilepsy resisting drug has adverse effect.

Description

technical field [0001] The invention relates to a small peptide with neuroprotective effect, which belongs to the technical field of biomedicine. Background technique [0002] Epilepsy (Epilepsy) is a chronic central nervous system disease. It is a behavioral abnormality caused by sudden excessive and synchronous abnormal discharge of certain neuron groups in the central nervous system. It ranks first in the prevalence of six major central nervous system diseases today. third. At present, more than 50 million people worldwide suffer from epilepsy, and there are about 9 million epilepsy patients in my country, and 400,000 new cases are added every year in my country. Epilepsy causes mental disorders or mental retardation in patients, causing brain diseases, which seriously threatens the health and life safety of patients, and has serious negative effects on individuals, families and society. Epilepsy has become an important public health problem. [0003] Studies on animal ...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61K38/17A61K47/42A61P25/08
CPCA61K38/00A61P25/08C07K14/4702C07K2319/10
Inventor 颜景芝曹阳范江朋李冲尹晓慧陆丰
Owner XUZHOU MEDICAL UNIV