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Application of psoralen B in inhibiting abnormal aggregation of Tau protein

A psoralen and protein technology, applied in the field of biomedicine, can solve problems such as unsatisfactory drug efficacy, achieve the effects of less toxic and side effects, inhibiting abnormal aggregation of Tau protein, and good curative effect

Inactive Publication Date: 2019-01-25
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to overcome the above-mentioned deficiencies of the prior art, to provide a kind of psoralen B as the relevant inhibitor of abnormal aggregation of Tau protein or the application in medicine, to solve the existing problem of inhibiting abnormal aggregation of Tau protein and treating tau protein disease Technical Problems of Unsatisfactory Drug Effects in Clinical Medicine

Method used

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  • Application of psoralen B in inhibiting abnormal aggregation of Tau protein
  • Application of psoralen B in inhibiting abnormal aggregation of Tau protein
  • Application of psoralen B in inhibiting abnormal aggregation of Tau protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1: Inhibitory effect of different concentrations of psoralen on TauK18 protein fibrosis.

[0047] Because heparin sodium induces TauK18 protein to self-aggregate to form fibers. In order to simulate abnormal aggregation of Tau protein in the brain to form neurofibrillary tangles, in this embodiment, TauK18 protein was induced by heparin sodium to form abnormal aggregation to form neurofibrillary tangles. Thioflavin T (ThT) can interact with the β-sheet in the aggregated filaments to generate fluorescence, and its fluorescence intensity is positively correlated with the amount of fiber, which can be used for quantitative analysis of protein fiber amount.

[0048] Method: The purified TauK18 protein freeze-dried product was obtained, weighed accurately, dissolved in Tris-HCl Buffer (pH 7.4), and prepared into a protein mother solution of about 0.56 mg / mL, then quantified with BCA, and recorded the exact concentration. Precisely weigh psoralen B, prepare high-conc...

Embodiment 2

[0057] Example 2: Transmission electron microscope experiment of psoralen B inhibiting TauK18 protein fibrosis

[0058] Methods: The aggregation and fibrosis of TauK18 treated with different concentrations of psoralen B can be visually observed by transmission electron microscopy (TEM), which is a strong evidence for the ThT fluorescence experiment. From the ThT experiment of embodiment 1, collect DMSO control group, low concentration psoralen B group (1 μ M), middle concentration psoralen B group (10 μ M) and high concentration psoralen B group (50 μ M) respectively 5 μL of each sample was diluted and dripped onto the copper grid, and settled for 0.5 hours, then sucked off the excess sample with filter paper, and then dripped 5 μL of 3% uranyl acetate respectively, let it stand for 2 minutes, and then sucked up the excess with filter paper. of uranyl acetate. Place in a transmission electron microscope (NIPPON TEKNO, JEM-1230), observe at an accelerating voltage of 100kV, ta...

Embodiment 3

[0060] Example 3: Depolymerization of TauK18 protein fibers by psoralen B

[0061] Example 3 further verifies that psoralen B has depolymerization effect on TauK18 fibers.

[0062] Methods: Different concentrations of psoralen B were added to the reaction system that had formed fibers, and the depolymerization effect of psoralen B on TauK18 fibers was explored. Around the 19th hour of the fibrosis reaction, the fluorescence intensity reached the maximum, and the degree of TauK18 fibrosis remained basically unchanged. Specifically, according to the construction method of the previous ThT fluorescence experiment in Example 1 (Table 2), when the fluorescence intensity is observed to remain almost unchanged, the detection of the microplate reader is suspended, and 5 μL of different concentrations of psoralen are added to each system. B and an equal volume of DMSO were used as a control, and continued to be placed in a microplate reader at 37°C for 17 hours of constant temperature i...

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Abstract

The invention discloses the application of psoralen B as an inhibitor of abnormal aggregation of Tau protein and in the preparation of a drug for preventing / treating Tau protein disease, or a functional food or health product for preventing / alleviating Tau protein disease. The psoralen B is non-toxic, the psoralen B can be use as an anti-Tau protein disease drug for treating neurodegenerative disease. The psoralen B has the function of effectively inhibiting abnormal aggregation of the Tau protein, thereby preventing the pathological process of the Tau protein disease.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of psoralen B in drugs for inhibiting abnormal aggregation inhibitors of tau protein and preventing / treating tau protein diseases. Background technique [0002] In recent years, the number of elderly patients with neurodegenerative diseases has been increasing year by year, manifested as cognitive impairment, memory loss, behavior and motor ability weakening and so on. One of these protein deposits is neurofibrillary tangles in nerve cells, which are formed by abnormal aggregation and fibrillation of Tau protein, leading to structural changes, functional degeneration, and even apoptosis of neurons. More and more researchers believe that Tau protein is an effective target for neurodegenerative diseases. Common neurodegenerative diseases include Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, Pick's disease, Parkinson's...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/12A61P25/28A23L33/105
CPCA23L33/105A23V2002/00A61K31/12A61P25/28A23V2200/322A23V2250/2116
Inventor 肖时锋张默涵吴秋平
Owner SHENZHEN UNIV
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