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Peptides with Neuroprotective Effects and Applications

A technology for Alzheimer's disease and drugs, applied in the field of neurotoxic peptides, to achieve good neuroprotective effects, improve neurotoxicity, and maintain expression

Inactive Publication Date: 2017-05-31
徐州瀚祥生物科技研究院有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether endogenous ADDLs and EphB2 combine in situ in the hippocampal tissue of AD model mice remains to be studied.

Method used

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  • Peptides with Neuroprotective Effects and Applications
  • Peptides with Neuroprotective Effects and Applications
  • Peptides with Neuroprotective Effects and Applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Confirming the binding between endogenous ADDLs and EphB2 in the AD mouse model

[0030] Experiments have shown that synthetic ADDLs were found to co-immunoprecipitate with EphB2 in mature hippocampal neurons (Cisse, M., Nature 469, 47-52.2011), but endogenous ADDLs and EphB2 were not detected in the hippocampal tissue of AD model mice Whether in situ binding occurs remains to be studied. The present invention proves the combination of endogenous ADDLs and EphB2 in the hippocampal tissue of AD model mice through a large number of experiments.

[0031] The specific experimental method is:

[0032] 1. Sample preparation: The APP / PSN transgenic AD model mice were decapitated, and the bilateral hippocampus was quickly isolated, and frozen in liquid nitrogen for later use. The following operations were all carried out in an ice-water bath: take out the hippocampus from liquid nitrogen and add homogenization buffer, homogenize at a high speed with a homogenizer (1...

Embodiment 2

[0036] Example 2 Detection of the interaction site between ADDLs and EphB2

[0037] The work of Cisse et al. revealed that the FN domain of EphB2 is the key region for its binding to ADDLs (Cisse, M., Nature 469, 47-52.2011), but the specific amino acid sequence of EphB2 binding to ADDLs is still unclear. The present invention identifies the specific amino acid sequence that ADDLs binds to the FN structural domain of EphB2 through a large number of experiments and according to the detection test of the polypeptide array.

[0038] 1. Peptide array synthesis

[0039] Synthetic array protein information is as follows:

[0040] PSAPQAVISSVNETSLMLEWTPPRDSGGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSEYNATAIKSPTNTVQGLKAGAIYVFQFVRARTVAGYGRYSGKM.

[0041] A total of 203 AAs are designed in Overlapping format. Each polypeptide in the array has a length of 10 amino acids and is truncated at intervals of...

Embodiment 3

[0060] Example 3 pep-32 and pep-63 block the interaction between ADDLs and EphB2

[0061] 1. Hippocampal neuron culture: According to the method established by Gao Can et al. (Gao C, et al., JNeurochem.2006; 98:1664-1677), the hippocampus of 17-19-day-old fetal mice or E1 neonatal mice was cut. After crushing, the cells were digested with trypsin, and the resulting cells were cultured in serum-free medium containing B27 supplement for 18-21 days for the experiment.

[0062] 2. Preparation of ADDLs: According to the method of Ronicke et al. (Ronicke R, et al., NeurobioAging. 2011; 32:2219-2228), Aβ 1-42 Dissolve in HFIP first, store in -80°C refrigerator after aliquot evaporation, dissolve in DMSO 24h before use and dilute to serum-free medium, place in 4°C refrigerator for 24h, centrifuge at 14000g for 10min, the supernatant is soluble Aβ oligomerization Body ADDLs.

[0063] Freshly prepared 25ul ADDLs (final concentration 500nM) and 2.5g / ml four interfering peptides (final ...

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Abstract

The invention discloses a peptide and an application of the peptide in medicine for treating alzheimer disease. The amino acid sequence of the peptide is VFQVRARTVA or NGVTDQSPFS. After screening in a great deal of experimental researches, the peptides with the special amino acid sequence are preferably obtained; the experiment results show that the peptides pep32 and pep63 can be competitively combined with ADDLs, thus the combination of ADDLs and EphB2 can be effectively resisted, the degradation of EphB2 is resisted, and as a result, the expression of NMDAR (N Methyl D Aspartate Receptor) on synaptolemma is maintained, the neurovirulence of ADDLs is reduced, and the neuroprotective effect is achieved. The peptide can be used for preparing neuroprotective drugs, or drugs for preventing and / or treating alzheimer disease, and has a good application prospect in the field of nerve treatment.

Description

technical field [0001] The invention relates to a peptide with neuroprotective effect, in particular to a peptide capable of improving neurotoxicity mediated by ADDLs, which can be used for preparing and preventing Alzheimer's disease, and belongs to the technical field of biomedicine. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia (senile dementia), is a central nervous system degenerative disease characterized by progressive mental decline, and its exact pathogenesis is still unclear. In recent years, more and more studies have shown that soluble β-amyloid (amyloidβ-peptide, Aβ) oligomers, also known as Aβ-derived diffusible ligands (Aβ-derived diffusible ligands, ADDLs) are the key to the etiology of AD molecular. At present, ADDLs have become a popular target for the treatment of AD. Targeting ADDLs therapy can not only improve the early symptoms of AD, but also may delay the progress of AD. Targeting ADDLs to study therapeutic st...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06A61K38/08A61P25/28
Inventor 高灿石小东孙凯孙楠郝景茹胡蕊
Owner 徐州瀚祥生物科技研究院有限公司
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