课题基金基金详情
ZAG调节线粒体功能和GLUT3活性参与癫痫神经元能量代谢障碍形成的机制
结题报告
批准号:
82001367
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
刘熙
依托单位:
学科分类:
神经电活动异常与发作性疾病
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
刘熙
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中文摘要
癫痫中存在与发病及预后相关的神经元能量代谢障碍,表现为ATP合成降低和葡萄糖摄取减少,但具体机制不明。我们前期研究发现,癫痫降低神经元锌-α2-糖蛋白(ZAG),而升高ZAG可减轻癫痫发作及葡萄糖摄取障碍。ZAG可进入线粒体影响呼吸链和F0F1-ATP合成酶,并通过胰岛素样生长因子1受体(IGF1R)促进葡萄糖转运体3(GLUT3)摄取葡萄糖。目前尚无ZAG在癫痫神经元代谢障碍中作用的研究。我们推测:癫痫神经元中ZAG降低可抑制呼吸链和F0F1-ATP合成酶合成ATP,并通过IGF1R抑制GLUT3摄取葡萄糖。本研究拟从分子、细胞及动物水平,明确ZAG在癫痫神经元能量代谢障碍中的作用;探讨ZAG调节神经元ATP合成和GLUT3葡萄糖摄取的机制;探索癫痫神经元葡萄糖摄取与ATP合成之间的关系。本课题将从ZAG这个新靶点探讨癫痫神经元能量代谢障碍的发生机制,为癫痫的防治提供新思路。
英文摘要
Neuronal energy metabolic dysfunction characterized by reduced ATP production and glucose uptake exists in epilepsy , and is related to epileptogenesis and prognosis. However, the specific mechanism of this neuronal energy metabolic dysfunction is unclear. In our preliminary study, we found that epilepsy significantly reduced neuronal zinc-α2-glycoprotein (ZAG) level, while overexpressing ZAG relieved seizure and glucose uptake dysfunction. ZAG could enter mitochondria and affect respiratory chain and F0F1-ATP synthase, and ZAG could also promote glucose uptake through glucose transporter 3 (GLUT3) via regulating insulin-like growth 1 receptor (IGF1R). There is no report on the effect of ZAG on neuronal energy metabolic dysfunction in epilepsy. Based on these evidence, we speculated that, in epilepsy, reduction of neuronal ZAG inhibits ATP synthesis by suppressing respiratory chain and F0F1-ATP synthase, it also inhibits glucose uptake through GLUT3 via suppressing IGF1R. This study planned to investigate the role of ZAG in neuronal energy metabolic dysfunction in epilepsy, to explore the mechanism by which ZAG regulate neuronal ATP synthesis and glucose uptake, and to clarify the relation between neuronal glucose uptake and ATP synthesis. This study aims to explore the mechanism of neuronal energy metabolic dysfunction in epilepsy based on ZAG, a novel target, which may provide new insight into the prevention and treatment of epilepsy.
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DOI:10.1007/s13760-023-02355-2
发表时间:2023
期刊:Acta Neurologica Belgica
影响因子:--
作者:Yuke Zhong;Hang Liu;Changhong Tan;Xi Liu;Lifen Chen
通讯作者:Lifen Chen
The Efficacy and Safety of Pharmacological Treatments for Restless Legs Syndrome: Systemic Review and Network Meta-Analysis.
不宁腿综合征药物治疗的有效性和安全性:系统评价和网络荟萃分析
DOI:10.3389/fnins.2021.751643
发表时间:2021
期刊:Frontiers in neuroscience
影响因子:4.3
作者:Zhou X;Du J;Liang Y;Dai C;Zhao L;Liu X;Tan C;Mo L;Chen L
通讯作者:Chen L
Glucose transporter 3 in neuronal glucose metabolism: Health and diseases
神经元葡萄糖代谢中的葡萄糖转运蛋白 3:健康与疾病
DOI:10.1016/j.metabol.2021.154869
发表时间:2021-08-27
期刊:METABOLISM-CLINICAL AND EXPERIMENTAL
影响因子:9.8
作者:Peng, Wuxue;Tan, Changhong;Chen, Lifen
通讯作者:Chen, Lifen
Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment.
Fyn 激酶调节高糖 (HG) 治疗的动物和细胞模型中的多巴胺能神经元凋亡
DOI:10.1186/s12860-021-00398-y
发表时间:2021-12-04
期刊:BMC molecular and cell biology
影响因子:2.8
作者:Tan C;Liu X;Zhang X;Peng W;Wang H;Zhou W;Jiang J;Mo L;Chen Y;Chen L
通讯作者:Chen L
DOI:10.1177/17474930221145259
发表时间:2022-12-21
期刊:INTERNATIONAL JOURNAL OF STROKE
影响因子:6.7
作者:Tan, Changhong;Zhao, Lili;Chen, Lifen
通讯作者:Chen, Lifen
ZAG调节神经元葡萄糖摄取和ATP合成参与癫痫能量代谢障碍的机制
  • 批准号:
    --
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2021
  • 负责人:
    刘熙
  • 依托单位:
国内基金
海外基金