Deferasirox exerts anti-epileptic effects by improving brain iron homeostasis via regulation of ITPRIP
作者全名：Duan, Xinhao; Han, Huifang; Liu, Jing; Qiu, Yu; Wang, Yi; Wu, Xiaotian; Zhang, Hui; Zou, Zhen; Qiu, Jingfu; Chen, Chengzhi; Xiao, Fei; Tian, Xin
作者地址：[Duan, Xinhao; Han, Huifang; Qiu, Jingfu] Chongqing Med Univ, Sch Publ Hlth, Dept Hlth Lab Technol, Chongqing 400016, Peoples R China; [Liu, Jing; Zhang, Hui; Xiao, Fei; Tian, Xin] Chongqing Med Univ, Chongqing Key Lab Neurol, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China; [Liu, Jing] Chongqing Univ Three Gorges Hosp, Dept Neurol, Chongqing 404100, Peoples R China; [Qiu, Yu] Chongqing Med Univ, Univ Town Hosp, Dept Neurol, Chongqing 401331, Peoples R China; [Wang, Yi] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Key Lab Neuropharmacol & Translat Med Zhejiang Pro, Hangzhou 310053, Peoples R China; [Xiao, Fei; Tian, Xin] Chongqing Med Univ, Key Lab Major Brain Dis & Aging Res, Minist Educ, Chongqing 400016, Peoples R China; [Wu, Xiaotian] Chongqing Med Univ, Dept Clin Lab, Univ Town Hosp, Chongqing 401331, Peoples R China; [Zou, Zhen] Chongqing Med Univ, Inst Life Sci, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China; [Chen, Chengzhi] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China
通信作者：Xiao, F; Tian, X (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Neurol, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China.; Xiao, F; Tian, X (通讯作者)，Chongqing Med Univ, Key Lab Major Brain Dis & Aging Res, Minist Educ, Chongqing 400016, Peoples R China.; Chen, CZ (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China.
来源：NEUROCHEMISTRY INTERNATIONAL
ESI学科分类：NEUROSCIENCE & BEHAVIOR
WOS号：WOS:001223659200001
JCR分区：Q1
影响因子：4.4
年份：2024
卷号：176
期号：
开始页：
结束页：
文献类型：Article
关键词：Epilepsy; Deferasirox; Iron; ITPRIP
摘要：Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.
基金机构：National Science Foundation of China [82001378]; China Postdoctoral Science Foundation [2023M730443]; Natural Science Foundation of Chongqing [CSTB2023NSCQ-JQX0035, CSTB2022NSCQ-LZX0038, cstc2021ycjh-bgzxm0035]; Joint Project of Chongqing Health Commission and Science and Technology Bureau [2023QNXM009]; Science and Technology Research Program of Chongqing Education Commission [KJQN202200435, KJQN202100438]
基金资助正文：This work was supported by grants from the National Science Foundation of China (82001378) , China Postdoctoral Science Foundation (2023M730443) , Natural Science Foundation of Chongqing (CSTB2023NSCQ-JQX0035, CSTB2022NSCQ-LZX0038, cstc2021ycjh-bgzxm0035) , the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2023QNXM009) , Science and Technology Research Program of Chongqing Education Commission (KJQN202200435, KJQN202100438).
