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Application of P2Y4 receptor stimulant in preparing medicaments for treating Alzheimer's disease

An Alzheimer's and receptor agonist technology, which is applied in the application field of P2Y4 receptor agonists in the preparation of drugs for the treatment of Alzheimer's disease, and achieves the effects of good application prospects, low toxicity and low risk

Inactive Publication Date: 2011-05-18
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] So far, there are no literature reports and patent publications showing the effect of P2Y4 receptor agonists on microglia pinocytosis, and there are no reports and patent publications showing that P2Y4 receptor agonists mediated microglia Potential application value of pinocytosis in the treatment of Alzheimer's disease

Method used

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  • Application of P2Y4 receptor stimulant in preparing medicaments for treating Alzheimer's disease
  • Application of P2Y4 receptor stimulant in preparing medicaments for treating Alzheimer's disease
  • Application of P2Y4 receptor stimulant in preparing medicaments for treating Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: ATPγS can induce microglia to produce large vesicles.

[0052] (1) Experimental materials:

[0053] Cells: microglia were isolated and cultured from SD (Sprague-Dawley) neonatal rats. SD neonatal rats were provided by the Animal Management Center of the Institute of Neurology, Chinese Academy of Sciences.

[0054] Reagent: ATPγS was purchased from Sigma, USA, product number A-1388. L-15, MEM medium, fetal bovine serum and HBSS were purchased from Gibco, USA. PDL (Poly D-lycine) was purchased from Sigma, USA.

[0055] Instruments: Migration experiment equipment, consisting of phase contrast microscope, stimulator, drug delivery valve, micromanipulator, and heating plate; cell culture equipment, including dissecting mirror, cell culture flask, and incubator, etc.

[0056] (2) Experimental method:

[0057] Cell culture: The primary culture of microglia was according to the method described by D.Giulian et al. 1986 with slight modifications. The modified cu...

Embodiment 2

[0063] Example 2: The micron-sized vesicles induced by ATPγS are pinocytic vesicles

[0064] (1) Experimental materials:

[0065] Cells: Primary cultured microglia.

[0066] Reagent: recombinant rat GM-CSF (recombinant rat Granulocyte-macrophage colony-stimulating factor) was purchased from American R&D Company, the product number is 518-GM-005. FD70S (Fluorescein-Dextran, molecular weight 70kd) was purchased from Invitrogen Company of the United States, and the product number is D1823. ATPγS was purchased from Sigma Company of the United States, the article number is A-1388.

[0067] Instrument: confocal fluorescence microscope. Cell culture equipment, including dissecting mirrors, cell culture flasks, and incubators, etc.

[0068] (2) Experimental method:

[0069] GM-CSF induces pinocytosis: treat microglial cells with MEM medium supplemented with FD70S (2 μg / μl) and GM-CSF (200 U / ml) for 5 minutes, wash cells with HBSS two to three times, and place in confocal fluoresc...

Embodiment 3

[0078] Example 3: P2Y 4 Receptor may mediate ATPγS-induced pinocytosis of microglia

[0079] (1) Experimental materials:

[0080] Cells: Primary cultured microglia.

[0081] Reagent: RB-2 (Reactive Blue 2) was purchased from RBI Company in the United States, and the article number was R-115. Suramin, ATPγS, ATP, and UTP were purchased from Sigma, USA, with article numbers S-2671, A-1388, A-7699, and U-6875, respectively. Anti-P2Y 4 Antibodies and Anti-P2Y 2 Antibodies were purchased from Hong Kong Abcam Company, the product numbers are ab-13108 and ab-46537, respectively. FD70S and fTD70S (fixable Texasred-Dextran, molecular weight 70kd) were purchased from Invitrogen Company of the United States, and the product numbers were D-1823 and D-1864.

[0082] Instrument: confocal fluorescence microscope. Cell culture equipment, including dissecting mirrors, cell culture flasks, and incubators, etc.

[0083] (2) Experimental method:

[0084] Antagonist experiment: cells were...

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Abstract

The invention provides application of a P2Y4 receptor stimulant in preparing medicaments for treating the Alzheimer's disease. The application of the P2Y4 receptor stimulant in preparing medicaments for treating the Alzheimer's disease has the beneficial effects that the P2Y4 receptor stimulant can be used for effectively promoting the pinocytosis to beta-amyloid polypeptide of microglial cells so as to relieve and even cure the Alzheimer's disease; and the P2Y4 receptor stimulant has lower toxicity and low risk and is clinically applied to treating various diseases, thus the P2Y4 receptor stimulant has good application prospect in treating the Alzheimer's disease.

Description

(1) Technical field [0001] The present invention relates to P2Y 4 Application of receptor agonist in preparation of medicine for treating Alzheimer's disease. (2) Background technology [0002] Alzheimer's disease is senile dementia, which is a progressive neurodegenerative disease. Its clinical manifestations are continuous degeneration of cognitive and memory functions, decreased ability of daily life, and various neuropsychiatric symptoms and behaviors. obstacle. As of 2009, there were more than 35 million Alzheimer's patients worldwide, and this number is expected to quadruple to more than 100 million by 2050. This widespread neurological disease not only brings great suffering to patients and their families, but also becomes the fourth leading cause of death in the elderly population. However, there is no effective medical method to cure this disease so far. [0003] Through the efforts of scientists in recent decades, people have understood the cause of Alzheimer's...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/7076A61P25/28
Inventor 段树民李慧泉陈聪
Owner ZHEJIANG UNIV
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