P2X4 receptor participates in autophagy regulation in Parkinson’s disease  

作　　者：Xue Zhang Jing Wang Jin-Zhao Gao Xiao-Na Zhang Kai-Xin Dou Wan-Da Shi An-Mu Xie 

机构地区：[1]Department of Neurology,Affiliated Hospital of Qingdao University,Qingdao,Shandong Province,China [2]Neurological Regulation Institute of Qingdao University,Qingdao,Shandong Province,China

出　　处：《Neural Regeneration Research》2021年第12期2505-2511,共7页中国神经再生研究（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China,Nos.81571225 and 81971192(both to AMX).

摘　　要：Dysfunctional autophagy often occurs during the development of neurodegenerative diseases,such as Parkinson’s disease,Huntington’s disease,and Alzheimer’s disease.The purinergic P2X4 receptor is an ATP-gated ion channel that is widely expressed in the microglia,astrocytes,and neurons of the central and peripheral nervous systems.P2X4R is involved in the regulation of cellular excitability,synaptic transmission,and neuroinflammation.However,the role played by P2X4R in Parkinson’s disease remains poorly understood.Rat models of Parkinson’s disease were established by injecting 6-hydroxydopamine into the substantia nigra pars compacta.P2X4R-targeted small interfering RNA(siRNA)was injected into the same area 1 week before injury induction to inhibit the expression of the P2X4 receptor.The results showed that the inhibition of P2X4 receptor expression in Parkinson’s disease model rats reduced the rotation behavior induced by apomorphine treatment,increased the latency on the rotarod test,and upregulated the expression of tyrosine hydroxylase,brain-derived neurotrophic factor,LC3-II/LC3-I,Beclin-1,and phosphorylated tropomyosin receptor kinase B(TrkB)in brain tissue,while simultaneously reducing p62 levels.These findings suggest that P2X4 receptor activation might inhibit neuronal autophagy through the regulation of the brain-derived neurotrophic factor/TrkB signaling pathway,leading to dopaminergic neuron damage in the substantia nigra and the further inhibition of P2X4 receptor-mediated autophagy.These results indicate that P2X4 receptor might serve as a potential novel target for the treatment of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Affiliated Hospital of Qingdao University(approval No.QYFYWZLL26119)on April 12,2016.

关 键 词：6-HYDROXYDOPAMINE APOMORPHINE brain-derived neurotrophic factor dopaminergic neurons neuron degeneration P2X4R Parkinson’s disease TRKB AUTOPHAGY 

分 类 号：R453[医药卫生—治疗学] R741[医药卫生—临床医学]