Qu Xiaochong, Lai Xiaodan, He Mingfeng, Zhang Jinyuan, Xiang Binbin, Liu Chuqiao, Huang Ruina, Shi Yiwu, Qiao Jingda
Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.
School of Health Management, Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2024 Dec 16;21(1):195-211. doi: 10.4103/NRR.NRR-D-24-00877.
Complex genetic architecture is the major cause of heterogeneity in epilepsy, which poses challenges for accurate diagnosis and precise treatment. A large number of epilepsy candidate genes have been identified from clinical studies, particularly with the widespread use of next-generation sequencing. Validating these candidate genes is emerging as a valuable yet challenging task. Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy, due to its rapid reproduction rate, powerful genetic tools, and efficient use of ethological and electrophysiological assays. Here, we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes, including genetic tools for manipulating target gene expression, ethological assays for seizure-like behaviors, electrophysiological techniques, and functional imaging for recording neural activity. We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes. We summarize well- established precision medicine strategies for epilepsy and discuss prospective treatment options, including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model. Finally, we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.
复杂的遗传结构是癫痫异质性的主要原因，这给准确诊断和精准治疗带来了挑战。从临床研究中已鉴定出大量癫痫候选基因，尤其是随着下一代测序技术的广泛应用。验证这些候选基因正成为一项有价值但具有挑战性的任务。果蝇因其繁殖速度快、遗传工具强大以及在行为学和电生理学检测中的高效应用，成为验证与癫痫等神经遗传疾病相关候选基因的理想动物模型。在此，我们系统地总结了用于研究癫痫基因的果蝇模型的优势技术，包括用于操纵靶基因表达的遗传工具、用于类似癫痫发作行为的行为学检测、电生理技术以及用于记录神经活动的功能成像。然后，我们介绍了几种鉴定癫痫基因的典型策略，并为多基因病因癫痫中的基因 - 基因相互作用提供了新见解。我们总结了已确立的癫痫精准医学策略，并讨论了前瞻性治疗方案，包括基于果蝇模型的遗传性癫痫的药物治疗和基因治疗。最后，我们还探讨了遗传咨询和辅助生殖技术作为预防遗传性癫痫的潜在方法。
