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Application of oligo-guluronic acid in drugs for prevention and treatment of Tau protein diseases

A technology of guluronic acid and oligomerization, applied in the field of biomedicine, can solve problems such as unsatisfactory drug efficacy, achieve prevention/treatment of tau protein disease, inhibit cell endoplasmic reticulum stress activity, and inhibit hyperphosphorylation of tau protein the effect of

Inactive Publication Date: 2019-08-23
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The purpose of the present invention is to overcome the above-mentioned deficiencies of the prior art, to provide a kind of oligomeric guluronic acid as the application in Tau protein disease-related inhibitors or medicines, to solve the clinical efficacy of existing drugs for the treatment of Tau protein diseases suboptimal technical issues

Method used

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  • Application of oligo-guluronic acid in drugs for prevention and treatment of Tau protein diseases
  • Application of oligo-guluronic acid in drugs for prevention and treatment of Tau protein diseases
  • Application of oligo-guluronic acid in drugs for prevention and treatment of Tau protein diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Preparation of GOS and Identification of Polymerization Degree

[0050] This embodiment provides a kind of preparation method of oligomeric guluronic acid, the specific preparation method is as follows:

[0051] Sodium alginate was dissolved in 0.5M HCl, heated at 90°C for 7h and then allowed to stand overnight to separate layers. Then centrifuge at 3500rpm at low speed for 10min to obtain the precipitate for later use; use 8% NaHCO for precipitation 3 After the solution is dissolved, adjust the pH to 2.85 with HCl, let it stand for stratification, centrifuge at 3500rpm at low speed for 10 minutes, collect the precipitate, dissolve it in water, and freeze-dry to prepare PG; weigh a certain amount of PG and dissolve it in PBS, add a certain amount of alginate to crack Enzyme, react at a constant temperature at 37°C for 2 hours, then add an equal amount of enzyme solution, and continue to react at 37°C for 24 hours; after the reaction is completed, heat in a w...

Embodiment 2

[0054] Example 2. The experiment of GOS reducing the phosphorylation level of Tau protein in HEK293 / Tau cells:

[0055] Method: HEK293 / Tau cells (2×10 6 cells / well) attached to the wall in a 6-well plate, after 4-6 hours, discard the supernatant, add 0.1mg / mL, 1mg / mL GOS to treat for 24h, use the cell lysate to extract the total protein, and then use the Western Blot method to detect the total protein The expression levels of Tau protein and phosphorylated Tau protein.

[0056] Results: The results of detecting the expression of total Tau protein were as follows: figure 1 As shown, the results of detecting the expression level of phosphorylated Tau protein are as follows figure 2 shown. Depend on figure 1It can be seen that the overexpressed Tau protein in HEK293 / Tau cells can be significantly down-regulated after GOS treatment. Depend on figure 2 It can be seen that after HEK293 / Tau cells were treated with GOS, the phosphorylation levels of Tau protein at serine 396 a...

Embodiment 3

[0057] Example 3. GOS inhibits thapsigargin-induced endoplasmic reticulum stress experiment:

[0058] Methods: The high expression of endoplasmic reticulum chaperone Grp78 (Bip) and C / EBP homologous protein transcription factor (CHOP) is an important manifestation of endoplasmic reticulum stress. In HEK293 / Tau cells induced by thapsigargin, the effect of GOS on the expression of Bip and CHOP was detected by Western Blot. HEK293 / Tau cells (2×10 6 per well) attached to the wall in a 6-well plate, after 4-6 hours, discard the supernatant, add 0.1 mg / mL, 1 mg / mL GOS to treat for 12 hours, add 2 μg / mL thapsigargin to stimulate for 12 hours, and then extract the total protein. Using Western Blot method, it was found that the endoplasmic reticulum stress of HEK293 / Tau cells induced by GOS-treated thapsigargin was as follows: image 3 shown. Depend on image 3 It can be seen that thapsigargin can effectively induce the expression of Bip and CHOP in HEK293 / Tau cells; after GOS trea...

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Abstract

The invention discloses an oligo-guluronic acid as an inhibitor for inhibiting at least one of total Tau protein expression, Tau protein hyperphosphorylation and endoplasmic reticulum stress activity,and application of the oligo-guluronic acid in preparation of drugs. The disclosed oligo-guluronic acid has the functions of effectively inhibiting the total Tau expression level, Tau protein phosphorylation, endoplasmic reticulum stress activity and the like, and correspondingly the pathological process of Tau protein diseases is prevented. In addition, because the oligo-guluronic acid is free of toxicant, the oligo-guluronic acid can be used as a drug resisting the Tau protein diseases in treatment of neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of an oligomeric guluronic acid in drugs for preventing and treating tauopathies. Background technique [0002] With the increasing degree of population aging, the number of patients with neurodegenerative diseases is increasing year by year, seriously endangering the health and quality of life of the elderly, and bringing heavy mental and economic pressure to the families of patients. Therefore, it is of great significance to research and develop effective drugs for the prevention or treatment of neurodegenerative diseases. [0003] 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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/702A61K31/715A61P25/00A61P25/28
CPCA61K31/702A61K31/715A61P25/00A61P25/28
Inventor 续旭李梅婷毕德成蔡楠杨朋姚丽君
Owner SHENZHEN UNIV
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