Neuropsychiatric Disease and Treatment (Jun 2020)
Can Maternal Autoantibodies Play an Etiological Role in ASD Development?
Abstract
Iva Dudova,1 Klara Horackova,2 Michal Hrdlicka,1 Martin Balastik3 1Department of Child Psychiatry, Charles University Second Faculty of Medicine, Prague, Czech Republic; 2Department of Psychiatry, Charles University First Faculty of Medicine, Prague, Czech Republic; 3Laboratory of Molecular Neurobiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech RepublicCorrespondence: Iva DudovaDepartment of Child Psychiatry, Charles University Second Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague 15006, Czech RepublicTel +420 224 433 458Fax +420 224 433 420Email [email protected]: 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.Keywords: maternal autoantibodies, autism spectrum disorder, animal models, CRMP2, therapy
