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A brain-penetrating polypeptide and its application in the preparation of drugs for preventing and treating senile dementia

A technology for senile dementia and drugs, applied in the field of medicine, to achieve the effect of easy induction of expression purity and no toxic side effects

Active Publication Date: 2021-10-08
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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  • A brain-penetrating polypeptide and its application in the preparation of drugs for preventing and treating senile dementia
  • A brain-penetrating polypeptide and its application in the preparation of drugs for preventing and treating senile dementia
  • A brain-penetrating polypeptide and its application in the preparation of drugs for preventing and treating senile dementia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Synthesis of TAT-siP-DC

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

[0073] TAT-siP-DC synthetic HPLC report

[0074]

[0075] The purity of the synthesized TAT-siP-DC polypeptide is 97.14%, 1 mg per tube, 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 prepare it for immediate use.

Embodiment 2

[0077] Polypeptide TAT-siP-DC interferes with the binding of DAPK1 and β-catenin. See figure 2 .

[0078] The peptide was synthesized by Shanghai Qiangyao Company. Co-immunoprecipitation with DAPK1 antibody showed that the combination of DAPK1 and β-catenin did not change when the polypeptide was not administered; in the presence of the polypeptide, the combination of DAPK1 and β-catenin was interfered. Co-immunoprecipitation with β-catenin antibody further confirmed that TAT-siP-DC can interfere with the combination of DAPK1 and β-catenin. At the same time, it also proved that the peptide we synthesized is effective.

Embodiment 3

[0080] Application of TAT-siP-DC in animal models of Alzheimer's disease

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

[0082]Pattern segregation, a more complex hippocampus-associated memory, is impaired through established patterns in early AD patients. The situational fear chamber includes a shock generator (AniLab, which can deliver a shock of 0.1 to 1.0 mA) and is linked to a computer. The soundproof box is equipped with lights and a small fan (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 the B room we used is that there is a 100% alcohol solution of benzaldehyde (0.25% concentration) at the bottom of the A room, and the side wall of the B room is inwardly formed at an angle of 60°, and the A room uses odorless 5% hydrogen Wipe with sodium oxide solution, and room B with pungent 1% acetic...

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PUM

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Abstract

The invention discloses a small molecular polypeptide TAT-siP-DC and its application in the preparation of medicines for treating or preventing senile dementia. The fusion protein polypeptide TAT-siP-DC, TAT, which utilizes artificially synthesized TAT protein transduction domain and siP-DC The siP-DC protein polypeptide can be taken up by neurons through the blood through the blood-brain barrier, and it can be applied to the in vivo Alzheimer's model, which can effectively exert its biological effect of blocking the combination of β-catenin and DAPK1, thus effectively Reversing the accumulation / phosphorylation of β-catenin, and improving the presynaptic swelling damage, long-term potentiation inhibition, and pattern separation disorder in Alzheimer's disease model animals can be used to prepare drugs for treating or preventing Alzheimer's disease.

Description

technical field [0001] The invention belongs to the field of medicine and relates to medicines for preventing and treating senile dementia, in particular to the application of small molecule polypeptides in the preparation of medicines 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 spectrum of cognitive impairment, including prominent impairment of episodic memory, usually at an early age. Pathologically, there are two hallmarks in the AD brain, 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 accumulating evidence suggests that overloaded Aβ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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