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Medicine for improving activity of midbrain substantia nigra dopamine neurons to preventing Parkinson disease

A Parkinson's disease and neuron technology, applied in the field of biomedicine, can solve the problems of no fulvestrant, loss of ability to produce dopamine, and reduced buffering capacity of exogenous dopamine drugs, so as to save time and overcome limitations Effect

Active Publication Date: 2019-12-13
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, with the continuous development of PD and continuous levodopa administration, the ability of the remaining dopaminergic neurons to produce dopamine is lost, and the buffering ability of exogenous dopamine drugs is reduced.
There are no reports related to the treatment of fulvestrant and Parkinson's disease

Method used

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  • Medicine for improving activity of midbrain substantia nigra dopamine neurons to preventing Parkinson disease
  • Medicine for improving activity of midbrain substantia nigra dopamine neurons to preventing Parkinson disease
  • Medicine for improving activity of midbrain substantia nigra dopamine neurons to preventing Parkinson disease

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Experimental program
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Embodiment 1

[0032] This embodiment provides a method for screening and improving the activity of dopamine neurons in the substantia nigra of the midbrain to prevent and treat Parkinson's disease, comprising the following steps:

[0033] S1. Gene expression data collection:

[0034] Gene expression data were obtained from public GEO data. GEO datasets contain microarray, next-generation sequencing, and other forms of high-throughput genomic data submitted by research scholars. From GEO, we downloaded 6 genome-wide gene expression data sets, namely gene expression data of 10 brain regions (GSE60862), spatiotemporal gene expression data (GSE25219), normal human brain tissue gene expression data (GSE45878, GSE34865) , Parkinson's disease case-control gene expression data (GSE8397) and mouse brain gene expression data (GSE16496).

[0035] S2. Construction of normal human brain co-expression network:

[0036]A gene co-expression network was constructed using the GSE60862 dataset. Genes in 1...

Embodiment 2

[0059] Example 2 Fulvestrant cell experiment proof

[0060] 1. Fulvestrant can inhibit the down-regulation of PD gene

[0061] The rotenone-induced Parkinson's disease model in Step 7 of Example 1 was used to verify the effect of fulvestrant on the PD gene. In the rotenone-induced Parkinson's disease model, the inventors treated cortical neurons with five treatments of DMSO, CCCP, ROT400nM, ROT400nM+FUL200nM and FUL200nM. First, cortical neurons were pretreated with 200nm rotenone for 2 hours, and then treated with different concentrations (100nm, 200nm and 300nm) of fulvestrant for 24 hours. Cortical neurons treated with CN (control group), DMSO (2%), rotenone and different concentrations (100nM, 200nM and 300nM) of fulvestrant were detected by RT-qPCR method. The purpose of the DMSO treatment was to test the effect of the solvent. Statistical analysis was performed using GraphPad Prism 7.0 software.

[0062] The result is as figure 1 As shown, after treating the Parkins...

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Abstract

The invention provides a medicine for improving the activity of midbrain substantia nigra dopamine neurons to preventing a Parkinson disease. The medicine is fulvestrant. The invention also provides amethod for screening the medicine for improving the activity of midbrain substantia nigra dopamine neurons to preventing the Parkinson disease. A bioinformatics method using a weighted gene co-expression network to analyze and identify a biologically-related differential co-expression module, matches genes closely related to the Parkinson disease to a gene network module so as to obtain a gene co-expression module related to the Parkinson disease, and by a correlation map database and different gene expression profile data between midbrain substantia nigra encephalic region samples in a normal control group from a Parkinson patient, screens out a medicine that can significantly reverse the abnormally expressed genes in the module. The method overcomes the limitation of a single pathway ortarget, and also uses the CMAP database to screen approved clinical medicines, saves time, money, and labor costs, and is more conducive to the development of safe and effective medicines.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to screening a drug for improving the activity of dopamine neurons in the substantia nigra of the midbrain and preventing and treating Parkinson's disease through bioinformatics methods. Background technique [0002] Parkinson's disease (PD) is a degenerative disease of the central nervous system characterized by degeneration and necrosis of dopamine neurons in the substantia nigra of the midbrain. Increased height, slow movement, etc. Although PD has been studied for nearly 200 years, so far, due to the unclear pathogenesis of PD, no matter whether drug therapy or surgical treatment can only improve the symptoms of the disease, it cannot prevent the development of the disease, let alone prevent it. cure. [0003] Pathologically, the degeneration of dopamine (DA) neurons in the substantia nigra reticular zone and the decrease of striatal DA levels can be seen in the pathology...

Claims

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Application Information

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IPC IPC(8): G16B20/20G16H70/40A61K31/565A61P25/16
CPCG16B20/20G16H70/40A61K31/565A61P25/16
Inventor 赵慧英范世超
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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