Department of Pediatrics, University of Chieti-Pescara, Sant'Annunziata Hospital, 66100 Chieti, Italy.
Department of Neonatology, University of L'Aquila, San Salvatore Hospital, 67100 L'Aquila, Italy.
Int J Mol Sci. 2024 Nov 7;25(22):11982. doi: 10.3390/ijms252211982.
Neurodevelopmental disorders (NDDs) are a group of conditions affecting brain development, with variable degrees of severity and heterogeneous clinical features. They include intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), often coexisting with epilepsy, extra-neurological comorbidities, and multisystemic involvement. In recent years, next-generation sequencing (NGS) technologies allowed the identification of several gene pathogenic variants etiologically related to these disorders in a large cohort of affected children. These genes encode proteins involved in synaptic homeostasis, such as SNARE proteins, implicated in calcium-triggered pre-synaptic release of neurotransmitters, or channel subunit proteins, such as post-synaptic ionotropic glutamate receptors involved in the brain's fast excitatory neurotransmission. In this narrative review, we dissected emerged molecular mechanisms related to NDDs and epilepsy due to defects in pre- and post-synaptic transmission. We focused on the most recently discovered SNAREopathies and AMPA-related synaptopathies.
神经发育障碍（NDDs）是一组影响大脑发育的疾病，其严重程度和临床表现存在差异。它们包括智力障碍（ID）、自闭症谱系障碍（ASD）、注意力缺陷/多动障碍（ADHD），这些疾病通常伴有癫痫、神经外共病和多系统受累。近年来，下一代测序（NGS）技术使得在一大群受影响的儿童中，能够确定与这些疾病相关的几个基因致病性变异。这些基因编码涉及突触稳态的蛋白质，如 SNARE 蛋白，其参与钙触发的神经递质前突释放，或通道亚基蛋白，如参与大脑快速兴奋性神经传递的突触后离子型谷氨酸受体。在这篇叙述性综述中，我们剖析了由于前突触和后突触传递缺陷而导致的与 NDDs 和癫痫相关的新兴分子机制。我们重点关注最近发现的 SNARE 病和 AMPA 相关突触病。
