Ma Qing, Chen Guang, Li Ying, Guo Zhenming, Zhang Xue
NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Harbin Medical University, Harbin, Heilongjiang 150000, China.
Department of Urology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China.
Genes Dis. 2023 Jul 16;11(5):101021. doi: 10.1016/j.gendis.2023.04.041. eCollection 2024 Sep.
Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.
皮质发育畸形（MCD）是一组发育障碍，其特征是由遗传或有害环境因素导致的皮质结构异常。多种MCD是由基因变异引起的。MCD是智力残疾和难治性癫痫的常见病因。随着成像和测序技术的快速发展，MCD的诊断率不断提高，许多导致MCD的潜在基因也相继被发现。然而，MCD的高遗传异质性使得理解其分子发病机制和确定有效的靶向药物具有挑战性。因此，在本综述中，我们概述了皮质发育的重要事件。然后，我们重点围绕PI3K/PTEN/AKT/mTOR信号通路阐述MCD分子遗传学研究的进展。最后，我们简要讨论了MCD的诊断方法、疾病模型和治疗策略。这些信息将有助于对MCD进行进一步研究。了解PI3K/PTEN/AKT/mTOR信号通路在MCD中的作用可能会为治疗MCD相关疾病带来新策略。
