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Application of Muscone in preparing medicine for treating Alzheimer disease

A technology of Alzheimer's disease and muscone, which is applied in the application field of the compound muscone as a drug for the preparation of Alzheimer's disease, can solve the problems of non-specific HDACi substrates, toxic side effects, etc., and reduce neuron death Effect

Inactive Publication Date: 2017-06-06
NANJING DRUM TOWER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, non-specific HDACi has a wide range of substrates, so it may cause serious side effects

Method used

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  • Application of Muscone in preparing medicine for treating Alzheimer disease
  • Application of Muscone in preparing medicine for treating Alzheimer disease
  • Application of Muscone in preparing medicine for treating Alzheimer disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] In vitro studies have proved that Mus inhibits the neurotoxicity of Aβ and induces neuronal apoptosis to have a therapeutic effect on AD:

[0053] 1) Materials and methods

[0054] Primary cortical neuron culture: 15-17d pregnant C57BL / 6J(B6) mice were sacrificed by neck dislocation, and the embryos were taken, placed in a petri dish filled with pre-cooled PBS, the cerebral cortex was separated, and digested with 1X trypsin , cultured in polylysine-coated culture plates, 1×10 5 cells / ml, partly change the medium every 2-3 days, and co-culture for 8-10 days. The cells were cultured in a serum-free, phenol red-free and estrogen-free medium (Neurobasal plus Hepes, B27 and glutamine), in a 5% CO2 incubator at 37°C.

[0055] Detection of neuronal cell viability: the cell viability was detected by tetramethylazolate colorimetric method (MTT method). Add MTT to 100 μl of culture solution / well, continue culturing in an incubator at 37°C with 5% CO2 for 4 hours, then pour off a...

Embodiment 2

[0062] In vitro studies have shown that Mus can inhibit Aβ-induced neuronal apoptosis:

[0063] This part of the study is to further confirm that Mus can inhibit apoptosis by regulating the protein expression levels of apoptosis regulators Bcl-2 and Bax.

[0064] 1) Materials and methods

[0065] Quantitative determination of Bcl-2 and Bax contents in neuronal cells by Western blot: extract protein, dissolve in 5Xloading Buffer, and boil for 5 minutes. Perform electrophoresis on a 4-20% polyacrylamide gel, and transfer the protein to a PVDF membrane. Block with 5% skimmed milk for 1 hour at room temperature. Add primary antibodies rabbit anti-Bcl-2 (1:1000, Cell signaling technology), rabbit anti-Bax (1:1000, Cell signaling technology), rabbit anti-GAPDH (1:5000, Bioworld technology), overnight at 4°C , horseradish peroxidase-labeled secondary antibody (1:5000, Bioworld) combined for 2 hours, and its protein expression was determined by enhanced chemiluminescence.

[0066]...

Embodiment 3

[0069] In vivo studies demonstrate that Mus has a therapeutic effect on APP / PS1 mice:

[0070] B6C3-Tg (APPswe / PSEN1dE9) transgenic mice (abbreviated as APP / PS1) were used as animal models of AD and treated with intraperitoneal injection of Mus. Behavioral evidence shows that Mus has a therapeutic effect on AD.

[0071] 1) Materials and methods

[0072] B6C3-Tg (APPswe / PSEN1dE9) transgenic mice, referred to as APP / PS1 for short, were used as AD animal models. The experiment was randomly divided into 3 groups: APP / PS1 littermate wild-type mice, APP / PS1 transgenic mice, APP / PS1 mice+ Mus was injected intraperitoneally at 2 mg / kg, once a day, for 15 days, with 8 mice in each group.

[0073] Behavioral testing: the water maze test is a recognized method for testing the learning and memory ability of animals. Morris water maze: the diameter of the circular pool is 122cm, the height is 75cm, the platform height is 50cm, the diameter is 10cm, the platform is 1cm below the water sur...

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PUM

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Abstract

The invention discloses study on application of Muscone which is called as Mus for short in preparing a medicine for treating Alzheimer disease through modern biological technologies and bioinformatic analysis. The Mus is found to have an effect of restraining A beta neurovirulence and can reduce nerve cell death, so that the Muscone can be prepared into injection preparations for treating the Alzheimer disease to be used for treating the Alzheimer disease. The injection preparation for treating the Alzheimer disease is prepared by mixing Muscone compound 2%(v / v) ethyl alcohol and 98%(v / v) normal saline according to 500mu g to 1000mu l, and in-vivo intraperitoneal injection dose of the injection preparation is 2mg / Kg / day.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to the application of compound Muscone (Mus for short) as a medicine for treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a progressive degenerative disease of the central nervous system, and its main clinical features are progressive memory and cognitive dysfunction. The prevalence rate of people over the age of 65 is about 5%, and the prevalence rate of people over the age of 85 is 20%. AD has become the fourth cause of death after heart disease, malignant tumors, and stroke, bringing heavy burdens to families and society. burden. [0003] Studies have shown that learning and memory-related synapse formation and remodeling are closely related to chromatin remodeling, and the important role of histone acetylation in cognitive function has attracted more and more attention. Histone acetylation homeostasis is regulated b...

Claims

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Application Information

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IPC IPC(8): A61K31/122A61K9/08A61K47/10A61P25/28
CPCA61K31/122A61K9/0019A61K9/08A61K47/10
Inventor 徐运杨卉陈易简于林杰
Owner NANJING DRUM TOWER HOSPITAL
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