Application of CHCHHD10 in promoting AChR subunit gene expression and maintaining NMJ stability.

A gene expression and subunit technology, applied in the field of application of CHCHD10 in promoting AChR subunit gene expression and maintaining NMJ stability, can solve the problem of unknown neurotransmission

Active Publication Date: 2020-11-17
ZHEJIANG UNIV
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Although CHCHD10 has been shown to regulate mitochondrial structure and function, whether and h

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  • Application of CHCHHD10 in promoting AChR subunit gene expression and maintaining NMJ stability.
  • Application of CHCHHD10 in promoting AChR subunit gene expression and maintaining NMJ stability.
  • Application of CHCHHD10 in promoting AChR subunit gene expression and maintaining NMJ stability.

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[0031] The technical solution of the present invention will be described in further detail below in conjunction with the accompanying drawings. It should be noted that the specific implementation is only a detailed description of the present invention and should not be regarded as a limitation of the present invention. In the following examples, the reagents or instruments used can be purchased from commercial channels, 1M=1mol / L. Unless otherwise specified, the image processing in the present invention uses PowerPoint, Adobe Photoshop CS5, and ImageJ software; the electrophysiological data is mainly analyzed using Clampfit 9.2 (Molecular Devices). Statistical analysis mainly uses Excel 2010 and GraphPad Prism 5 software for statistical processing. Data analysis mainly used two-tailed paired, two-tailed unpaired t-test, analysis of variance, and the data representation method was Mean±SEM. Statistically significant differences are indicated as *p<0.05, **p<0.01 and ***p<0.001...

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Abstract

The invention discloses an application of CHCHHD10 in promoting AChR subunit gene expression and maintaining NMJ stability. According to the invention, the regulation effect of CHCHD10 in skeletal muscle on NMJ steady state is explored through experimental technical means such as immunohistochemistry, electrophysiology, electron microscopy, behavioristics and the like; the ATP level of cells or tissues can be reduced by silencing or knocking out the CHCHD10 gene, and the generation of ATP is prompted to depend on the expression of CHCHD10; the fact that ATP can promote AChR aggregation inducedby Agrin is further proved; a chromatin immunoprecipitation experiment shows that ATP can promote the combination of a transcription factor GABP alpha and a promoter of an AChR subunit gene; the ATPis prompted to promote AChR aggregation induced by Agrin by promoting AChR subunit gene expression, so that the normal function of the NMJ is maintained; the invention suggests that targeting NMJ maybe an important means for early treatment and intervention of ALS and other neuromuscular diseases.

Description

technical field [0001] The present invention specifically relates to the application of CHCHD10 in promoting AChR subunit gene expression and maintaining NMJ stability. Background technique [0002] Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease. One of the main features is the gradual loss of control of the motor neurons in the spinal cord to the skeletal muscles, clinically manifested by progressive atrophy and weakness of the muscles, followed by the involvement of the respiratory muscles, and eventually the patient died of respiratory failure. The survival period of ALS patients after clinical diagnosis is generally only 3-5 years, the incidence rate of the population is about 5 / 10000, most of them are sporadic ALS, and about 5-10% of patients are familial hereditary ALS. At present, the pathogenic mechanism of ALS mainly involves neuronal excitotoxicity, impaired RNA metabolism, protein misfolding, mitochondrial dysfunction, motor neur...

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Application Information

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IPC IPC(8): G01N33/68C12Q1/6851
CPCG01N33/6887C12Q1/6851G01N2800/2835G01N2333/47C12Q2531/113C12Q2565/125C12Q2563/107
Inventor 沈承勇肖亚涛张建敏张克兢
Owner ZHEJIANG UNIV
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