Application of chchd10 in promoting achr subunit gene expression and maintaining nmj stability

Abstract

The invention discloses the application of CHCHD10 in promoting AChR subunit gene expression and maintaining NMJ stability. The present invention explores the regulatory effect of CHCHD10 on NMJ homeostasis in skeletal muscle through immunohistochemistry, electrophysiology, electron microscopy and behavioral experimental techniques; silencing or knocking out the CHCHD10 gene can cause a decrease in the ATP level of cells or tissues, suggesting that ATP The production depends on the expression of CHCHD10; it is further confirmed that ATP can promote the aggregation of AChR induced by Agrin; through chromatin immunoprecipitation experiments, ATP can promote the combination of transcription factor GABPα and the promoter of AChR subunit gene; this suggests that ATP through Promote the expression of AChR subunit genes, and then promote the aggregation of AChR induced by Agrin, so as to maintain the normal function of NMJ; the present invention suggests that targeting NMJ may be 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...

AI Technical Summary

Problems solved by technology

Although CHCHD10 has been shown to regulate mitochondrial structure and function, whether and how CHCHD10 regulates neurotransmission between motor neurons and skeletal muscle remains unknown

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