AMPK role in epilepsy: a promising therapeutic target?
文献类型：期刊论文
| 作者 | Qi, Yingbei2,3,4; Zhang, Yong-mei2,3,4; Gao, Ya-nan1,3; Chen, Wen-gang1,3; Zhou, Ting2,3; Chang, Liuliu2,3; Zang, Yi3 ; Li, Jia2,3,4
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| 刊名 | JOURNAL OF NEUROLOGY
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| 出版日期 | 2023-11-27 |
| 页码 | 24 |
| 关键词 | AMPK Epilepsy Neuron Modulation Metabolism Ion Channels mTOR |
| ISSN号 | 0340-5354 |
| DOI | 10.1007/s00415-023-12062-w |
| 英文摘要 | Epilepsy is a complex and multifaceted neurological disorder characterized by spontaneous and recurring seizures. It poses significant therapeutic challenges due to its diverse etiology and often-refractory nature. This comprehensive review highlights the pivotal role of AMP-activated protein kinase (AMPK), a key metabolic regulator involved in cellular energy homeostasis, which may be a promising therapeutic target for epilepsy. Current therapeutic strategies such as antiseizure medication (ASMs) can alleviate seizures (up to 70%). However, 30% of epileptic patients may develop refractory epilepsy. Due to the complicated nature of refractory epilepsy, other treatment options such as ketogenic dieting, adjunctive therapy, and in limited cases, surgical interventions are employed. These therapy options are only suitable for a select group of patients and have limitations of their own. Current treatment options for epilepsy need to be improved. Emerging evidence underscores a potential association between impaired AMPK functionality in the brain and the onset of epilepsy, prompting an in-depth examination of AMPK's influence on neural excitability and ion channel regulation, both critical factors implicated in epileptic seizures. AMPK activation through agents such as metformin has shown promising antiepileptic effects in various preclinical and clinical settings. These effects are primarily mediated through the inhibition of the mTOR signaling pathway, activation of the AMPK-PI3K-c-Jun pathway, and stimulation of the PGC-1 alpha pathway. Despite the potential of AMPK-targeted therapies, several aspects warrant further exploration, including the detailed mechanisms of AMPK's role in different brain regions, the impact of AMPK under various conditional circumstances such as neural injury and zinc toxicity, the long-term safety and efficacy of chronic metformin use in epilepsy treatment, and the potential benefits of combination therapy involving AMPK activators. Moreover, the efficacy of AMPK activators in refractory epilepsy remains an open question. This review sets the stage for further research with the aim of enhancing our understanding of the role of AMPK in epilepsy, potentially leading to the development of more effective, AMPK-targeted therapeutic strategies for this challenging and debilitating disorder. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; GATED CALCIUM-CHANNELS ; METFORMIN TREATMENT ; SURFACE EXPRESSION ; SIGNALING PATHWAY ; ALPHA-SUBUNITS ; BETA-SUBUNITS ; MTOR PATHWAY ; RAT-BRAIN ; GLUCOSE |
| 资助项目 | National Natural Science Foundation of China[81,971,265] ; National Natural Science Foundation Of China[81,971,265] ; National Natural Science Foundation of China |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:001118748600001 |
| 出版者 | SPRINGER HEIDELBERG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308380]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zang, Yi; Li, Jia |
| 作者单位 | 1.China Pharmaceut Univ, Nanjing 210009, Jiangsu, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qi, Yingbei,Zhang, Yong-mei,Gao, Ya-nan,et al. AMPK role in epilepsy: a promising therapeutic target?[J]. JOURNAL OF NEUROLOGY,2023:24. |
| APA | Qi, Yingbei.,Zhang, Yong-mei.,Gao, Ya-nan.,Chen, Wen-gang.,Zhou, Ting.,...&Li, Jia.(2023).AMPK role in epilepsy: a promising therapeutic target?.JOURNAL OF NEUROLOGY,24. |
| MLA | Qi, Yingbei,et al."AMPK role in epilepsy: a promising therapeutic target?".JOURNAL OF NEUROLOGY (2023):24. |
入库方式： OAI收割
来源：上海药物研究所
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