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Application of fungus polyketide in preparation of medicine used for treating alzheimer disease

A technology for Alzheimer's disease and fungal polyketides, applied in the field of application of fungal polyketides as drugs for the preparation of Alzheimer's disease

Inactive Publication Date: 2013-11-20
THE AFFILIATED DRUM TOWER HOSPITAL MEDICAL SCHOOL OF NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the excitotoxicity caused by NMDA receptor activation is involved in the pathological process of brain injury in various central nervous system diseases. In addition, the specificity of memantine needs to be further verified clinically.

Method used

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  • Application of fungus polyketide in preparation of medicine used for treating alzheimer disease
  • Application of fungus polyketide in preparation of medicine used for treating alzheimer disease
  • Application of fungus polyketide in preparation of medicine used for treating alzheimer disease

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] In vivo studies have demonstrated that TL-2 has a therapeutic effect on AD mice induced by Aβ deposition:

[0072] Inject oligomeric Aβ into the bilateral hippocampus of male ICR mice to make AD mouse models, and treat them with intraperitoneal injection of TL-2. It has been proved by behavioral studies that TL-2 has a therapeutic effect on AD.

[0073] 1) Materials and methods

[0074] The oligomeric Aβ was injected into the bilateral hippocampus of male ICR mice to create an AD animal model. The experiment was randomly divided into 3 groups: normal ICR mice, Aβ-induced AD mice, Aβ-induced AD mice+TL-2 (Nanjing University, Nanjing, China) by intraperitoneal injection of 10 mg / kg, once a day, for 15 days, with 12 mice in each group.

[0075] Behavioral testing: the water maze test is a recognized method for testing the learning and memory abilities of animals. Morris water maze: the diameter of the circular pool is 122cm, the height is 75cm, the platform height is 50c...

Embodiment 2

[0079] In vitro studies have proved that TL-2 inhibits the neurotoxicity of Aβ and induces neuronal apoptosis to have a therapeutic effect on AD:

[0080] 1) Materials and methods

[0081] Culture of primary cortical neurons: Pregnant 15-17d wild-type Kunming mice were sacrificed by neck dislocation, and the embryos were collected and placed in a petri dish filled with cold PBS, and the cerebral cortex was separated, digested with 1X trypsin, and placed in a polymer Cultured in culture plate after lysine treatment, 4×10 5 Cells / ml, partly change the medium every 2-3d, and co-culture for 8-10d. 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.

[0082] Human neuroblastoma cell culture: Human neuroblastoma cells, namely SH-SY5Y cells, were purchased from ATCC in the United States and grown in a medium containing 10% fetal bovine serum, 2mmol / L L-glutamine, penicillin (100...

Embodiment 3

[0092] In vitro studies have demonstrated that TL-2 activates the AKT / GSK3β signaling pathway to inhibit apoptosis:

[0093] In this part of the study, in order to further confirm that TL-2 inhibits apoptosis by regulating the AKT / GSK3β signaling pathway, the AKT inhibitor LY294002 and the GSK3β mutant plasmid GSK-3β-S9A will be used.

[0094] 1) Materials and methods

[0095] Quantitative determination of p-AKT, AKT, p-GSK3β, and GSK3β content in SH-SY5Y cells by Western blot: extract protein, then 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 antibody rabbit anti-p-AKT (1:1000, Cell signaling), rabbit anti-AKT (1:1000, Cell signaling), rabbit anti-p-GSK3β (1:1000, Cell signaling), rabbit anti - GSK3β (1:1000, Cell signaling), overnight at 4°C, horseradish peroxidase-labeled secondary antibody (1:...

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Abstract

The invention relates to an application of fungus polyketide in preparation of a medicine used for treating alzheimer disease. According to the application, a fungus polyketide compound is prepared into an injection preparation used for treating the alzheimer disease, molecular weight of the fungus polyketide compound is 478.434Da, and 10mg / Kg injection preparation is intraperitoneally injected everytime; the fungus polyketide compound overcomes the defects that similar medicines in the past can not influence a pathological process and specificity can not be determined; a fungus polyketide compound injection medicine is adopted, is a small molecule compound, can penetrate through a blood brain barrier and can act on a pathological process of the alzheimer disease (AD), a decision for developing a medicine used for treating AD at present is met, an Abeta nerve toxic effect can be directly inhibited, and Abeta-induced nerve cell apoptosis is inhibited, namely nerve cell apoptosis is reduced by activating an Akt / GSK-3beta / beta-catenin signal channel.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to the application of fungal polyketide compounds (Da lesconols B, TL-2 for short) in the preparation of drugs for treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a progressive central nervous system degenerative disease, 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. The main pathological mechanism of AD is the deposition of Aβ in and out of nerve cells in the brain and the death of nerve cells caused by neurotoxicity. Amyloid precursor protein (APP) in AD brain is cleaved by β-secretase and γ-secretase to produce Aβ40 ...

Claims

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Application Information

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IPC IPC(8): A61K31/122A61K9/08A61P25/28
Inventor 徐运朱晓蕾谭仁祥王苏雷杨卉
Owner THE AFFILIATED DRUM TOWER HOSPITAL MEDICAL SCHOOL OF NANJING UNIV
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