Application of Nedd4-2 to parkinson's disease treatment

A disease and RNA interference technology, applied in the direction of medical preparations containing active ingredients, nervous system diseases, organic active ingredients, etc., to improve expression and reduce excitotoxic effects

Inactive Publication Date: 2016-05-04
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, there is no research involving the role of Nedd4-2 in the pathogenesis of P

Method used

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  • Application of Nedd4-2 to parkinson's disease treatment
  • Application of Nedd4-2 to parkinson's disease treatment
  • Application of Nedd4-2 to parkinson's disease treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Embodiment 1: Preparation of Parkinson's disease mouse model

[0074] Principle: Neurotoxin MPTP is catalyzed by monoamine oxidase B in astrocytes to form active metabolite MPP in vivo + , transported into neuron cells by dopamine transporter, inhibits mitochondrial respiratory chain complex I, and leads to degeneration of dopaminergic neurons. Therefore, we choose C57 / bl mice to inject MPTP intraperitoneally to prepare Parkinson's disease model. Glutamate transporters GLAST and GLT-1 are mainly expressed on astrocytes, and astrocytes can remove more than 90% of glutamate in the intercellular space through GLAST and GLT-1, thereby protecting neurons from For glutamate excitotoxic injury, this example mainly studies the expression and activity changes of glutamate transporters GLT-1 and GLAST in PD and related regulation mechanisms by establishing a PD model.

[0075] Methods: 12-week-old healthy male C57 / bl mice (body weight about 25-30g) were randomly divided into nor...

Embodiment 2

[0077] Example 2 Detection of mRNA expression levels of glutamate transporters and Nedd4-2 in various regions of the mouse brain

[0078] Method: The PD mouse model was produced by intraperitoneal injection of MPTP (the specific method was the same as in Example 1). On the third day after MPTP injection, and on the first and third day after PD model establishment, a certain amount of mice were taken respectively. The midbrain, striatum and cerebral cortex were separated, and the mRNA expressions of GLT-1, GLAST and Nedd4-2 in each part were detected by qPCR. Mean ± standard error. * p** p<0.01.

[0079] result:

[0080] figure 2 It was shown that in the midbrain, the expression level of GLT-1 mRNA in PD mice was significantly up-regulated 3 days after modeling.

[0081] image 3 It was shown that in the striatum, 3 days after MPTP injection, GLT-1 mRNA levels were significantly reduced in the PD group 1 day and 3 days after modeling, and GLAST and Nedd4-2 mRNA levels wer...

Embodiment 3

[0084] Example 3 Detection of GLT-1, GLAST, p-Nedd4-2 and Nedd4-2 protein expression levels in various regions of the mouse brain

[0085] Method: The PD mouse model was created by intraperitoneal injection of MPTP (the specific method is the same as in Example 1), on the third day (3d) after MPTP injection, and on the first day (5+1d) and third day after PD modeling (5+3d), take a certain amount of mice each, separate the midbrain, striatum and cerebral cortex, and detect the protein expression levels of GLT-1, GLAST, p-Nedd4-2 and Nedd4-2 in each part by Western blotting, and apply ImageJ software was used for statistical analysis of data. mean ± standard error, * p<0.05. The substantia nigra is the largest nuclei of the midbrain, but because the substantia nigra is small and difficult to obtain, in this experiment we isolated the midbrain and carried out corresponding detection. In addition, the expression of phosphorylated Nedd4-2 in the statistical graph is the percent...

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Abstract

The invention discloses application of Nedd4-2 to parkinson's disease treatment. It is found that the regulation effect on glutamate transporter from Nedd4-2 participates in attack of PD, significance of regulation abnormity of Nedd4-2 to the glutamate transporter in the PD attack process is focused on, interaction between Nedd4-2 and the glutamate transporter and the influence on the expression and the function of the glutamate transporter from the concentration and activity of N2dd4-2 are discussed at the animal model and cell experiment level, the molecule mechanism for adjusting the glutamate transporter by Nedd4-2 is analyzed, and it is approved that Nedd4-2 can serve as a target for treating PD. Gene treatment on parkinson's disease is directed, parkinson's disease resistant drugs are effectively screened, and Nedd4-2 has great significance in the life quality improvement of parkinson's disease patients.

Description

technical field [0001] The invention relates to the application of Nedd4-2 in the treatment of Parkinson's disease. Background technique [0002] Parkinson's disease is a common degenerative disease of the nervous system in middle-aged and elderly people. Clinically, it is mainly manifested by motor system symptoms such as resting tremor, bradykinesia, muscle rigidity, and abnormal posture and gait. In recent years, non-motor symptoms of Parkinson's disease have gradually attracted people's attention. These symptoms include not only autonomic dysfunction such as hyperhidrosis and constipation, but also cognitive impairment such as hyposmia, visual-spatial ability impairment, and memory loss, as well as anxiety and depression. Emotional disorders, but also mental disorders such as hallucinations and delusions, and severe cases are accompanied by dementia. [0003] The pathogenesis of Parkinson's disease is currently recognized as the degeneration and loss of dopamine (DA) ne...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/7105A61P25/16
CPCA61K45/06A61K31/7105
Inventor 瞿少刚吴晓娟张秀萍何小亮童辉纯张云龙孟行军张文龙
Owner SOUTHERN MEDICAL UNIVERSITY
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