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
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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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