典型文献
Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications
文献摘要：
Recent insights collectively suggest the important roles of lysyl oxidase(LysOX)in the path-ological processes of several acute and chronic neurological diseases,but the molecular regulatory mech-anisms remain elusive.Herein,we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons.Mechanistically,LysOX promotes ferroptosis-associated lipid peroxidation in neu-rons via activating extracellular regulated protein kinase(ERK)-dependent 5-lipoxygenase(Alox5)signaling.In addition,overexpression of LysOX via adeno-associated viral vector(AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage.Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile(BAPN)significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage,while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers.These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage.Sup-pressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.
文献关键词：
中图分类号：
作者姓名：
Xiaoyuan Mao;Xuan Wang;Mingzhu Jin;Qin Li;Jining Jia;Menghuan Li;Honghao Zhou;Zhaoqian Liu;Weilin Jing;Yanli Zhao;Zhong Luo
作者机构：
Department of Clinical Pharmacology,Xiangya Hospital,Central South University,Changsha 410008,China;Institute of Clinical Pharmacology,Central South University,Hunan Key Laboratory of Pharmacogenetics,Changsha 410078,China;Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha 410078,China;National Clinical Research Center for Geriatric Disorders,Changsha 410008,China;School of Life Science,Chongqing University,Chongqing 400044,China;Department of Gynecology and Obstetrics,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Division of Chemistry and Biological Chemistry,School of Physical and Mathematical Sciences,Nanyang Technological University,Singapore 637371,Singapore;Institute of Cancer Neuroscience,Medical Frontier Innovation Research Center,the First Hospital of Lanzhou University,the First Clinical Medical College of Lanzhou University,Lanzhou 730000,China
文献出处：
引用格式：
[1]Xiaoyuan Mao;Xuan Wang;Mingzhu Jin;Qin Li;Jining Jia;Menghuan Li;Honghao Zhou;Zhaoqian Liu;Weilin Jing;Yanli Zhao;Zhong Luo-.Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications)[J].药学学报（英文版）,2022(09):3513-3528
A类：
Alox5,LysOX,aminopropionitrile,bioresponsive
B类：
Critical,involvement,lysyl,oxidase,seizure,induced,neuronal,damage,through,ERK,dependent,ferroptosis,its,therapeutic,implications,Recent,insights,collectively,suggest,important,roles,processes,several,acute,chronic,neurological,diseases,but,molecular,regulatory,mech,anisms,remain,elusive,Herein,we,explore,ferroptotic,death,neurons,Mechanistically,promotes,associated,lipid,peroxidation,activating,extracellular,regulated,protein,kinase,lipoxygenase,signaling,In,addition,overexpression,adeno,viral,vector,AAV,gene,transfer,enhances,sensitivity,aggravates,hippocampal,Our,studies,show,that,pharmacological,inhibition,BAPN,significantly,blocks,thereby,alleviates,while,cardiotoxicity,neurotoxicity,could,further,be,reduced,encapsulation,amorphous,calcium,carbonate,nanocarriers,These,findings,unveil,previously,unrecognized,pathway,regulation,during,Sup,pressing,this,may,yield,restoring,injury
AB值：
0.578837
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