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Brain-penetrating polypeptide and application thereof in preparation of medicament for preventing and treating Alzheimer's disease

A technology for Alzheimer's disease, medicine, applied in the field of medicine

Active Publication Date: 2020-06-09
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no specific treatment drug and method at present, and the above-mentioned drugs can only slightly relieve the symptoms of patients with middle-advanced senile dementia or delay the progression of the disease

Method used

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  • Brain-penetrating polypeptide and application thereof in preparation of medicament for preventing and treating Alzheimer's disease
  • Brain-penetrating polypeptide and application thereof in preparation of medicament for preventing and treating Alzheimer's disease
  • Brain-penetrating polypeptide and application thereof in preparation of medicament for preventing and treating Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Synthesis of TAT-siP-DC

[0072] The sequence of TAT-siP-DC is shown in SEQ ID NO.1, which was artificially synthesized by Shanghai Qiangyao Biotechnology Co., Ltd. The synthesis report is shown below, and the chromatogram is shown in figure 1 shown.

[0073] TAT-siP-DC Synthetic HPLC Report

[0074]

[0075] The purity of the synthesized TAT-siP-DC polypeptide is 97.14%, each 1 mg is in the form of white powder, completely soluble in water, sealed and protected from light and stored at -20°C. Before use, dilute it with normal saline for injection according to the specified concentration, and use it now.

Embodiment 2

[0077] The polypeptide TAT-siP-DC interferes with DAPK1 and β-catenin binding. See figure 2 .

[0078] The peptides were synthesized by Shanghai Qiangyao Company. Co-immunoprecipitation with DAPK1 antibody showed that the binding of DAPK1 and β-catenin did not change in the absence of the peptide; the presence of the peptide interfered with the binding of DAPK1 and β-catenin. Co-immunoprecipitation with β-catenin antibody further confirmed that TAT-siP-DC can interfere with the binding of DAPK1 and β-catenin. At the same time, it is also proved that our synthesized peptides are effective.

Embodiment 3

[0080] Application of TAT-siP-DC in senile dementia animal model

[0081] (1) TAT-siP-DC ameliorated the pattern separation disorder in APP / PS1 mice. See image 3 .

[0082]Pattern dissociation, a more complex hippocampal-related memory, is impaired by established patterns in patients with early AD. The episodic fear room includes a shock generator (AniLab, which can deliver 0.1 to 1.0 mA shocks) and is linked to a computer. The soundproof box is equipped with lights and small fans (for ventilation and background sound). In addition, there are voltmeters and sound intensity meters to detect the intensity of the stimulus. The difference between the A room and B room we use is that the bottom of the A room is placed with a 100% alcohol solution of benzaldehyde (0.25% concentration), the side wall of the B room is at an angle of 60° inward, and the A room is made of odorless 5% hydrogen Sodium oxide solution was wiped, and room B was wiped with pungent 1% acetic acid solutio...

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Abstract

The invention discloses a small molecule polypeptide TAT-siP-DC and application thereof in preparation of a medicament for treating or preventing Alzheimer's disease. The TAT-siP-DC is a fusion polypeptide employing a synthetic TAT protein transduction domain and siP-DC, and TAT can carry the siP-DC polypeptide through blood and cross blood-brain barrier to be taken up by neurons. When applied toan Alzheimer's disease model, the TAT-siP-DC can effectively exert a biological effect of blocking binding of beta-catenin and DAPK1, thereby effectively reversing accumulation / phosphorylation of beta-catenin, and improving presynaptic swelling damage, long time potentiation inhibition, and pattern separation disorder exhibited by Alzheimer's disease model animals, thus the TAT-siP-DC can be usedfor the preparation of the medicament for treating or preventing Alzheimer's disease.

Description

technical field [0001] The invention belongs to the field of medicine, relates to a drug for preventing and treating senile dementia, and particularly relates to the application of a small molecular polypeptide in the preparation of a drug for preventing and treating senile dementia. Background technique [0002] Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases in the elderly, accounting for approximately two-thirds of dementia cases worldwide. Clinically, AD is characterized by a range of cognitive impairments, including prominent episodic memory impairment that usually occurs early. Pathologically, AD brains have two markers, senile plaques composed of overproduced β-amyloid (Aβ) and neurofibrillary tangles (NFTs) composed of abnormally hyperphosphorylated tau protein. Over the past century, efforts have been devoted to exploring the underlying mechanisms of memory deficits, and growing evidence suggests that overloaded Aβ in the brain may ...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61K38/16A61P25/28
CPCA61K38/00A61P25/28C07K14/00C07K2319/10
Inventor 朱铃强侯童瑶刘丹胡凡韦娜
Owner HUAZHONG UNIV OF SCI & TECH
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