TBN improves motor function and prolongs survival in SOD1G93A and TDP-43M337V mouse model of amyotrophic lateral sclerosis  

作　　者：HUANG Chun-hui LI Jun ZHANG Gui-liang LIN Ying-qi LI Cai-juan ZHENG Xiao SONG Xi-cheng HAN Bo-feng GUO Bao-jian TU Zhu-chi ZHANG Jun SUN Ye-wei WANG Yu-qiang YAN Sen ZHANG Zai-jun 

机构地区：[1]Institute of New Drug Research,Jinan University College of Pharmacy,Guangzhou 510632,China

出　　处：《中国药理学与毒理学杂志》2021年第9期647-648,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative dis⁃ease characterized by progressive loss of upper and lower motor neurons that results in skeletal muscle atrophy,weakness and paralysis.Oxida⁃tive stress plays a key role in the pathogenesis of ALS,including familial forms of the disease arising from mutation of the gene coding for superoxide dismutase 1(SOD1).Moreover,although the pathogenesis of ALS is unclear,the abnormal accumulation of TAR DNA-binding pro⁃tein of 43 ku(TDP-43)is a pathological feature that exists in almost all patients.Thus far,there is no drug that can cure ALS/FTLD.Tetramethyl⁃pyrazine nitrone(TBN)is a derivative of tetra⁃methylapyrazine,derived from the traditional Chinese medicine Ligusticum chuanxiong,which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases.TBN is currently under clinical investi⁃gation for several indications including a phaseⅡtrial of ALS.Here,we explored the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse model.METHODS In the SOD1G93A transgenic mouse model,TBN was administered to mice by intraperitoneal or intragastric injection after the onset of motor deficits.At the same time,we unilaterally and bilaterally injected the TDP-43M337V virus into the striatum of the WT mouse,and gave the TBN treatment after the mice developed a phenotype.After administering these two models for a period of time,we con⁃ducted behavioral tests,including rotarod test,balance beam test,climbing pole test,etc,to evaluate the efficacy of TBN on SOD1G93A and TDP-43M337V models.Furthermore,we explored the possible mechanism of action of TBN in the treatment of ALS through Western blotting and immunohistochemistry/immunofluorescence staining analysis.RESULTS In the SOD1G93A transgenic mouse model,TBN slowed the pro⁃gression of motor neuron disease as evidenced by improved motor performance,reduced spinal motor neuron loss and the associated glial response,and decreased skeletal muscl

关 键 词：amyotrophic lateral sclerosis tetra⁃methylpyrazine nitrone superoxide dismutase 1 

分 类 号：R744.8[医药卫生—神经病学与精神病学]