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Application of oligomannuronic acid in inhibition of total tau expression, phosphorylation and aggregation

A mannuronic acid and phosphorylation technology, applied in the field of biomedicine, can solve problems such as unsatisfactory drug efficacy, achieve the effects of inhibiting hyperphosphorylation and abnormal aggregation, preventing/treating tauopathies, and having less toxic and side effects

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 in the prior art, provide a kind of oligomannuronic acid as the application in Tau protein disease-related inhibitors or medicines, to solve the ineffectiveness of existing drugs for the treatment of Tau protein diseases in clinic. ideal technical questions

Method used

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  • Application of oligomannuronic acid in inhibition of total tau expression, phosphorylation and aggregation
  • Application of oligomannuronic acid in inhibition of total tau expression, phosphorylation and aggregation
  • Application of oligomannuronic acid in inhibition of total tau expression, phosphorylation and aggregation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1. The experiment of MOS inhibiting the aggregation of Tau protein induced by heparin in vitro:

[0054] Method: The oligomeric Tau protein was donated by Mr. Xiao Shifeng, School of Life and Marine Science, Shenzhen University. Tau protein + water, Tau protein + heparin were used as two groups of control groups, and the experimental group was: 200 μM oligomeric Tau protein was added to the black microplate, and then Thioflavin T, Tris-HCl buffer, heparin and 1mg / ml MOS. Using a full-wavelength fluorescent microplate reader, under the emission light of 440nm and the excitation light of 485nm, continuous detection was carried out for 20h, and the fluorescence values ​​of each group were obtained, and the fluorescence values ​​were used for drawing.

[0055] Results: Through this test, we know that in vitro, using heparin to induce the aggregation of Tau protein, adding MOS to the system can effectively inhibit the occurrence of Tau protein aggregation. The resu...

Embodiment 2

[0056] Example 2. MOS reduces the phosphorylation of Tau protein in primary neurons of HEK293 / Tau cells and TauP301L mice:

[0057] method:

[0058] a. MOS reduces the phosphorylation of Tau protein in HEK293 / Tau cells Method: Experimental group: HEK293 / Tau cells (2×10 6cells / well) attached to the wall in a 6-well plate, after 4-6 hours, discard the supernatant, add 1mg / ml MOS to treat for 24 hours, use cell lysate to extract total protein; control group: refer to the method of the experimental group, but do not add 1mg / ml MOS; the expression levels of total Tau and phosphorylated Tau protein detected by WesternBlot after completion.

[0059] b. MOS reduces the phosphorylation of Tau protein in the primary neurons of TauP301L mice. Method: Experimental group: Inoculate the primary neurons of TauP301L mice and wild-type mice on a 6-well plate (7×10 5 per hole), add 1mg / ml MOS to treat for 24h, use cell lysate to extract total protein; control group: refer to the method of th...

Embodiment 3

[0063] Example 3. Experiment of MOS inhibiting GSK-3β activity in primary neurons of TauP301L mice:

[0064] Method: Experimental group: the primary neurons of TauP301L mice and wild-type mice were inoculated on 6-well plates (7×10 5 per hole), after adding 1mg / ml MOS to treat for 24h, the effect of MOS on the phosphorylation levels of GSK-3β and Akt in the primary neurons of TauP301L mice was detected by Western Blot method; the control group: refer to the method of the experimental group, However, 1 mg / ml MOS was not added.

[0065] result:

[0066] Western Blot was used to detect the effect of MOS on the phosphorylation levels of GSK-3β and Akt in the primary neurons of TauP301L mice. Figure 4 shown. The experimental results showed that compared with the primary neurons of wild-type mice, the phosphorylation level of Akt in primary neurons of TauP301L mice was decreased, and the phosphorylation level of total GSK-3β and its tyrosine 216 site was increased. High, the ph...

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Abstract

The invention discloses an inhibitor of at least any one of expression of oligomannuronic acid as total Tau protein, hyperphosphorylation of Tau protein and aggregation of Tau protein, and applicationin preparation of medicine. The invention discloses that the mannose oligomeric acid has the expression level of effectively inhibiting total Tau, tau protein phosphorylation and Tau protein aggregation, thus blocking the pathological process of Tau proteinopathy. In addition, since oligomanuronic acid is non-toxic, oligomanuronic acid can be used as an anti-Tau proteinopathy drug in the treatment of neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to an application of oligomannuronic acid in inhibiting Tau protein aggregation, total Tau protein expression and hyperphosphorylation. Background technique [0002] Tauopathy is a common neurodegenerative disease, which is a kind of neurodegenerative disease caused by the pathological aggregation of neurofibrillary tangles (NFT) in the human brain. Tau protein is involved in the stabilization of microtubules and is primarily located in neurons of the central nervous system. When tau proteins have problems so that they no longer stabilize microtubules properly, they can lead to diseases such as traumatic brain injury, frontotemporal dementia, progressive supranuclear palsy, Pick's disease, Alzheimer's disease, and others. Therefore, an important pathological feature of tauopathies is the aggregation of hyperphosphorylated tau protein to form neurofibrillary tangles....

Claims

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Application Information

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IPC IPC(8): A61K31/7016A61K31/702A61K31/715A61P25/00A61P25/28
CPCA61K31/7016A61K31/702A61K31/715A61P25/00A61P25/28
Inventor 续旭顾粮毕德成赖秋娴李童蔡楠刘琼肖时锋都秀波
Owner SHENZHEN UNIV
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