Function application of SH2B adapter protein 1 in treating Parkinson's disease

A Parkinson's disease and protein technology, applied in gene therapy, peptide/protein components, medical preparations containing active ingredients, etc., can solve problems such as necrosis reduction, movement disorders, and inability to prevent DA neuron apoptosis in the substantia nigra , achieve the effect of inhibiting proliferation and activation, reducing the level, and improving the loss of dopaminergic neurons in the substantia nigra compact part of the midbrain

Pending Publication Date: 2018-03-16
胡军
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, clinical treatment still lacks effective means, and levodopa replacement therapy is mainly used. Although it can relieve the early symptoms of most patients, it cannot prevent the

Method used

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  • Function application of SH2B adapter protein 1 in treating Parkinson's disease
  • Function application of SH2B adapter protein 1 in treating Parkinson's disease
  • Function application of SH2B adapter protein 1 in treating Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Construction of SH2B1 knockout (KO) mice and neuron-specific SH2B1 overexpression (neuron-specific transgenic, NTg) mice.

[0020] The construction method of SH2B1 KO mice (129Sv / C57BL / 6 gene background) refers to the literature (Duan, C., et al. 2004. Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose tolerance. Mol. Cell. Biol. 24 :7435–7443.). Construct Myc-tagged full-length rat SH2B1β sequence (neuron-specific enolase promoter / rat growth hormone enhancer), construct the constructed sequence into a fertilized embryo (C57BL / 6J x SJL) by microinjection, and obtain neurons Meta-specific SH2B1 transgenic mice (Ren D1, et al. 2007 Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. 117(2):397-406. ).

Embodiment 2

[0022] Effects of SH2B1 knockout and neuron-specific overexpression on MPTP PD model mice

[0023] Male C57BL / 6J genetic background wild-type (WT), SH2B1 KO mice and neuron-specific SH2B1 NTg mice were housed in five cages, fed with standard feed, free to drink water, and kept at room temperature (24 ± 2) ℃, The humidity is 50%-60%, the ventilation is good, and the daily light and dark time are 12 hours each. Before the experiment was carried out, the mice needed to be adaptively fed in the above feeding system for 3 days. All animal experiments complied with guidelines. The animal experiment protocol was approved by the Animal Care and Ethics Committee of Nanjing Medical University.

[0024] Each species of mice (WT, KO and NTg) were randomly divided into two groups: control (Control) group and MPTP group. Control group: On the first day, the rats were injected with sterile normal saline four times at an interval of 2 hours, each time at 0.1 ml / 10 g, and the rats were sacr...

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Abstract

The invention discloses a function application of SH2B adapter protein 1 in treating Parkinson's disease. Through neuron-specific over-expression of the SH2B1, dopaminergic neuron loss of substantia nigra pars compacta in an MPTP-induced mouse can be obviously improved, and the level of dopamine in striatum can be increased; and the proliferation and the activation of astrocytes and microglia of the substantia nigra pars compacta can be inhibited. Based upon the research results, it is indicated that the SH2B1 can be used for preparing medicines for treating the Parkinson's disease. Accordingto the invention, the therapeutic effect of the SH2B1 in the Parkinson's disease is verified for the first time; therefore, the SH2B1 is huge in market value and social benefit.

Description

technical field [0001] The invention belongs to the technical field of Parkinson's disease treatment, and specifically relates to the application of SH2B adapter protein 1 (SH2B1) in the preparation of drugs for treating Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is a neurodegenerative disease with an incidence rate second only to Alzheimer's disease. As my country gradually enters an aging society, the incidence rate is expected to increase year by year. PD is caused by the progressive degeneration and death of dopamine (DA) neurons in the substantia nigra, resulting in a decrease in the absolute content of DA in the striatum, but the exact etiological mechanism is still unclear. Pathological mechanisms include impaired neuronal and glial cell function, axonal transmission dysfunction, glutamate excitotoxicity, hyperactive oxygen levels, impaired metabolic pathways, decreased mitochondrial energy production, increased formation or degradat...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/00A61K48/00A61P25/16G01N30/74
CPCA61K38/1709A61K45/00A61K48/00G01N30/74
Inventor 胡军刘源鲁明
Owner 胡军
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