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Use of indirubin derivative for preparing medicines for treating nerve retrograde affection

A technology for neurodegeneration and derivatives, used in neurological diseases, drug combinations, etc.

Inactive Publication Date: 2007-08-29
黎明涛 +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the JNK pathway is not a single signaling pathway that mediates apoptosis of dopamine neurons in the substantia nigra

Method used

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  • Use of indirubin derivative for preparing medicines for treating nerve retrograde affection
  • Use of indirubin derivative for preparing medicines for treating nerve retrograde affection
  • Use of indirubin derivative for preparing medicines for treating nerve retrograde affection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Indirubin derivatives (IO) have protective intervening effects on MPTP-induced apoptosis of dopaminergic neurons in the ventral substantia nigra of the C57 mouse model of Parkinson's disease

[0024] 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) is a white powder neurotoxin , can specifically destroy dopamine nerve cells, thereby damaging the nigrostriatal pathway in the brain, causing symptoms similar to Parkinson's disease in humans and animals. MPTP was made into the required concentration with physiological saline.

[0025] Referring to the experimental methods of Tatton N.A. and Kish S.J. (Neuroscience, 1997; 77:1037-1048), select male C 57 90 BL / 6N type mice were randomly divided into three dose groups of normal saline (NS) group, MPTP (M) group and MPTP+IO, 15 in each group. On the first day of the experiment, the IO group was injected intraperitoneally with 0.3mg / ml, 1mg / ml, and 3mg / ml 10ml / kg respectively, a...

Embodiment 2

[0047] Indirubin derivatives (IO) to 1-methyl-4-phenylpyridinium ion (1-methyl-4-phenylpyiridiniumion, MPP + )-induced apoptosis of dopaminergic neurons in the ventral substantia nigra of the midbrain in vitro

[0048] As shown in Figure 4, dopaminergic neurons in substantia nigra were cultured in vitro with 14-day-pregnant fetal mice. On day 7 of in vitro culture, use 10 μM MPP + Induces neuronal apoptosis. Specific tyrosine hydroxylase antibody detects TH positive cells (a) solvent control group, red fluorescence is TH positive cells; (b) 10μM MPP + Reduce the number of TH positive cells; IO 1μM (c) and 3μM (d) rescued the apoptosis of neurons. (Magnification: ×200).

[0049] MPP + Is the active metabolite of MPTP in the body, MPP + Inducible apoptosis of dopamine neurons in the ventral midbrain of fetal rats cultured in vitro.

[0050] The cell culture method of the reference (J Neurosci, 1998; 18 (13): 4929-37. Restor Neurol Neurosci. 2003; 21 (1-2): 29-37.), take t...

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Abstract

The present invention relates to an application of indirubin derivative (IO) in the preparation of medicine for curing neural retrograde disease, specially, it relates to an application of indirubin derivative in the preparation of medicine for curing Parkinson's disease. Said invention uses the indirubin derivative as inhibitor and utilizes three kinds of mediated and died kinases of JNK / CDK5 / GSK3 beta which are inhibited by said indirubin derivative as clear target to develop the invented new medicine.

Description

[technical field] [0001] The invention relates to the application of indirubin derivatives (IO) in the preparation of medicines for treating neurodegenerative diseases, especially the application in the preparation of medicines for treating Parkinson's disease. [Background technique] [0002] Parkinson's disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, striatum and nuclei. Programmed cell death (ie, apoptosis) plays an important role in the neuronal degeneration of Parkinson's disease. The clinical treatment of Parkinson's disease is mainly to give dopamine prodrug levodopa and peripheral decarboxylase inhibitors combined symptomatic treatment to relieve the symptoms of Parkinson's disease. In recent years, gene therapy and stem cell therapy for Parkinson's disease have also been hotly studied. However, due to the problems of target gene selection, carrier and gene controllability in g...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/404A61P25/16A61P25/00
Inventor 黎明涛韩怡凡陈汝筑李文明
Owner 黎明涛
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