Dudova Iva, Horackova Klara, Hrdlicka Michal, Balastik Martin
Department of Child Psychiatry, Charles University Second Faculty of Medicine, Prague, Czech Republic.
Department of Psychiatry, Charles University First Faculty of Medicine, Prague, Czech Republic.
Neuropsychiatr Dis Treat. 2020 Jun 3;16:1391-1398. doi: 10.2147/NDT.S239504. eCollection 2020.
Autism spectrum disorder (ASD) is a heterogeneous condition with multiple etiologies and risk factors - both genetic and environmental. Recent data demonstrate that the immune system plays an important role in prenatal brain development. Deregulation of the immune system during embryonic development can lead to neurodevelopmental changes resulting in ASD. One of the potential etiologic factors in the development of ASD has been identified as the presence of maternal autoantibodies targeting fetal brain proteins. The type of ASD associated with the presence of maternal autoantibodies has been referred to as maternal antibodies related to ASD (MAR ASD). The link between maternal autoantibodies and ASD has been demonstrated in both clinical studies and animal models, but the exact mechanism of their action in the pathogenesis of ASD has not been clarified yet. Several protein targets of ASD-related maternal autoantibodies have been identified. Here, we discuss the role of microtubule-associated proteins of the collapsin response mediator protein (CRMP) family in neurodevelopment and ASD. CRMPs have been shown to integrate multiple signaling cascades regulating neuron growth, guidance or migration. Their targeting by maternal autoantibodies could change CRMP levels or distribution in the developing nervous system, leading to defects in axon growth/guidance, cortical migration, or dendritic projection, which could play an etiological role in ASD development. In addition, we discuss the future possibilities of MAR ASD treatment.
自闭症谱系障碍（ASD）是一种具有多种病因和风险因素的异质性疾病，包括遗传和环境因素。最近的数据表明，免疫系统在产前脑发育中起重要作用。胚胎发育过程中免疫系统失调可导致神经发育变化，进而引发ASD。ASD发展的潜在病因之一已被确定为存在靶向胎儿脑蛋白的母体自身抗体。与母体自身抗体存在相关的ASD类型被称为与ASD相关的母体抗体（MAR ASD）。母体自身抗体与ASD之间的联系已在临床研究和动物模型中得到证实，但其在ASD发病机制中的具体作用机制尚未阐明。已确定了一些与ASD相关的母体自身抗体的蛋白质靶点。在此，我们讨论了塌陷反应介导蛋白（CRMP）家族的微管相关蛋白在神经发育和ASD中的作用。CRMP已被证明可整合多种调节神经元生长、导向或迁移的信号级联反应。母体自身抗体对它们的靶向作用可能会改变发育中的神经系统中CRMP的水平或分布，导致轴突生长/导向、皮质迁移或树突投射缺陷，这可能在ASD发展中起病因学作用。此外，我们还讨论了MAR ASD治疗的未来可能性。
