Epilepsy therapy beyond neurons:Unveiling astrocytes as cellular targets
Yuncan Chen1
Jiayi Hu1
Ying Zhang2
Lulu Peng1
Xiaoyu Li2
Cong Li3
Xunyi Wu1
Cong Wang4
1.Shanghai Fifth People's Hospital,School of Pharmacy,MOE Key Laboratory of Smart Drug Delivery,MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases,Department of Neurology,Huashan Hospital,Fudan University,Shanghai,China2.Department of Pharmacy,Zhongshan Hospital,Fudan University,Shanghai,China3.Shanghai Fifth People's Hospital,School of Pharmacy,MOE Key Laboratory of Smart Drug Delivery,MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases,Department of Neurology,Huashan Hospital,Fudan University,Shanghai,China;Shanghai Key Laboratory of Molecular Imaging,Shanghai University of Medicine and Health Sciences,Shanghai,China4.Shanghai Fifth People's Hospital,School of Pharmacy,MOE Key Laboratory of Smart Drug Delivery,MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases,Department of Neurology,Huashan Hospital,Fudan University,Shanghai,China;Shanghai Key Laboratory of Molecular Imaging,Shanghai University of Medicine and Health Sciences,Shanghai,China;Greater Bay Area Institute of Precision Medicine(Guangzhou),Fudan University,Shanghai,China;Key Laboratory of Biomedical Imaging Science and System,Chinese Academy of Sciences,Shenzhen,Guangdong Province,China
摘要：Epilepsy is a leading cause of disability and mortality worldwide.However,despite the availability of more than 20 antiseizure medications,more than one-third of patients continue to experience seizures.Given the urgent need to explore new treatment strategies for epilepsy,recent research has highlighted the potential of targeting gliosis,metabolic disturbances,and neural circuit abnormalities as therapeutic strategies.Astrocytes,the largest group of nonneuronal cells in the central nervous system,play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons,regulating neurotransmitter levels,and modulating synaptic plasticity.This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system.Building on previous research,we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects:the imbalance between excitatory and inhibitory neuronal signaling,dysregulation of metabolic homeostasis in the neuronal microenvironment,neuroinflammation,and the formation of abnormal neural circuits.We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy.We categorize the therapeutic targets proposed by these studies into four areas:restoration of the excitation-inhibition balance,reestablishment of metabolic homeostasis,modulation of immune and inflammatory responses,and reconstruction of abnormal neural circuits.These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy.Additionally,we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments.These limitations arise from interspecies differences between humans and animal models,as well as the complex comorbidities associated with epilepsy in humans.We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes,such as gene therapy and imaging strategies.The findings presented in this review may help open new therapeutic avenues for patients with drug-resistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
机标关键词：cellularbeyondastrocytesepilepsyneuronstargetstherapyunveiling
论文发表日期：2026-01-30
在线出版日期：2025-12-11（本平台首次上网日期，不代表文献的发表时间）
页数：16( 23-38 )
英文信息