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Application of NRG (neuregulin) 1beta1/ErbB4/Akt signal pathway in preparing or screening drug target for resisting Alzheimer disease neuronal loss

An Alzheimer's disease, neuron technology, applied in the fields of biotechnology and medicine, can solve problems such as strong side effects

Inactive Publication Date: 2014-03-26
XINXIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Drugs that have been approved for the treatment of Alzheimer's disease at home and abroad mainly include cholinesterase inhibitors and glutamate receptor antagonists, but these drugs have strong side effects

Method used

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  • Application of NRG (neuregulin) 1beta1/ErbB4/Akt signal pathway in preparing or screening drug target for resisting Alzheimer disease neuronal loss
  • Application of NRG (neuregulin) 1beta1/ErbB4/Akt signal pathway in preparing or screening drug target for resisting Alzheimer disease neuronal loss
  • Application of NRG (neuregulin) 1beta1/ErbB4/Akt signal pathway in preparing or screening drug target for resisting Alzheimer disease neuronal loss

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] This example tests the changes in the expression of NRG1β1 in different age groups, and analyzes the APP / PS1 double transgenic mice (TG mice) of NRG1β1 at different ages (1 month, 6 months, 12 months and 18 months). and the changes in the brain of wild-type mice (WT mice), the results are as follows figure 1 (A-D), where β-actin was used as an internal reference, and the data were expressed as mean±SEM. *P<0.05**P<0.01 and ***P<0.001 compared with the control group. The results showed that NRG1β1 levels were not statistically different between 1-month-old and 18-month-old TG and WT mice. In contrast, NRG1β1 was significantly increased in TG mice at 6 and 12 months of age, and the difference was statistically significant.

[0078] Aβ was obviously precipitated in the brain of 6-month-old AD mice, while figure 1 (A-D) The results showed that the endogenous NRG1β1 protein level of APP / PS1 double transgenic mice was significantly higher than that of WT mice at 6 and 12 m...

Embodiment 2

[0080] This example analyzes the influence of NRG1β1-ECD. APP / PS1 double transgenic mice and wild-type mice, 6 months old, were intraperitoneally injected with NRG1β1-ECD (50ng / kg / day, NRG1β1-ECD dissolved in 0.9% NaCl) as the treatment group and vehicle (0.9% NaCl) as the control group, treated for 14 days. Then Western blot was used to measure the expression of NRG1β1 in the brain tissue of APP / PS1 double transgenic mice and wild-type mice in the NRG1β1-ECD treatment group and the carrier control group, the results were as follows figure 1 (E-F). The results showed that after NRG1β1-ECD treatment, the expression of NRG1β1 in APP / PS1 double transgenic mice and wild-type mice in the treatment group was significantly increased, and the difference was statistically significant.

Embodiment 3

[0082] In this example, the effect of NRG1β1-ECD on the expression of ErbB4, p-ErbB4, Akt and p-Akt was determined by Western blot method for the APP / PS1 double transgenic mice in the NRG1β1-ECD treatment group and the carrier control group in Example 2 , the result is as figure 1 (G-H). The results indicated that NRG1β1-ECD resulted in a significant increase in the relative levels of p-ErbB4 / ErbB4 and p-Akt / Akt.

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Abstract

The invention discloses application of an NRG (neuregulin) 1beta1 / ErbB4 / Akt signal pathway in preparing or screening a drug target for resisting Alzheimer disease neuronal loss. Experiments discover the protection effect of the NRG1beta1 / ErbB4 / Akt in resisting neuronal loss in Alzheimer disease, the application firstly provides that NRG1beta1 plays the occurrence development process of resisting apoptosis in brain of Alzheimer disease by activating an ErbB4 receptor in brain, and a more specific novel target is provided to effective prevention, control or treatment of Alzheimer disease.

Description

technical field [0001] The invention relates to a use of NRG1β1 / ErbB4 / Akt signaling pathway as a drug target for preparing or screening anti-Alzheimer's disease neuron loss, and belongs to the fields of biotechnology and medicine. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is a degenerative disease of the central nervous system with an insidious onset and a chronic progressive course. It is the most common type of senile dementia. The main manifestations are neuropsychiatric symptoms such as progressive memory impairment, cognitive dysfunction, personality changes, and language barriers, which seriously affect social, occupational, and life functions. The etiology and pathogenesis of AD have not yet been elucidated, and the characteristic pathological changes are extracellular senile plaques formed by the deposition of β-amyloid protein, neurofibrillary tangles formed by hyperphosphorylation of tau protein, and neuron loss with gli...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K45/00A61K38/18A61P25/28
Inventor 崔卫刚闫建国任铭新张应花陶晶
Owner XINXIANG MEDICAL UNIV
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