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met-Controlled Allosteric Module of Neural Generation as A New Therapeutic Target in Rodent Brain Ischemia

Chinese Journal of Integrative Medicine 2021年第12期27卷 896-904页

作者： LI Kang-ning ZHANG Ying-ying YU Ya-nan WU Hong-li WANG Zhong Department of Traditional Chinese Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijing(100070)China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing(100700)China

Objective To investigate a met-controlled allosteric module(AM)of neural generation as a potential therapeutic target for brain *** We selected Markov clustering algorithm(MCL)to mine functional modules in the related target *** to the topological similarity,one functional module was predicted in the modules of baicalin(BA),jasminoidin(JA),cholic acid(CA),compared with I/R model *** functional module included three genes:Inppl1,met and dapk3(IMD).By gene ontology enrichment analysis,biological process related to this functional module was *** functional module participated in generation of *** blotting was applied to present the compound-dependent regulation of ***-immunoprecipitation was used to reveal the relationship among the three *** used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion *** expressions of vascular endothelial growth factor(VEGF)and matrix metalloproteinase 9(MMP-9)were supposed to show the changing circumstances for neural generation under cerebral *** Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group(P<0.05).Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory *** anti-ischemic excitatory allosteric module(AME)of generation of neurons(AME-GN)was validated successfully in *** neurons increased in BJC treatment group(P<0.05).The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group(P<0.05).Conclusions AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic *** novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cere

关键词： allosteric module inppm-met-dapk3 generation of neurons brain ischemia

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