Key Laboratory of Brain Functional Genomics (STCSM & MOE), Affiliated Mental Health Center (ECNU), School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China.
Shanghai Changning Mental Health Center, Shanghai 200335, China.
Cells. 2022 Nov 28;11(23):3815. doi: 10.3390/cells11233815.
Excitatory (glutamatergic) synaptic transmission underlies many aspects of brain activity and the genesis of normal human behavior. The postsynaptic scaffolding proteins SAP90/PSD-95-associated proteins (SAPAPs), which are abundant components of the postsynaptic density (PSD) at excitatory synapses, play critical roles in synaptic structure, formation, development, plasticity, and signaling. The convergence of human genetic data with recent in vitro and in vivo animal model data indicates that mutations in the genes encoding SAPAP1-4 are associated with neurological and psychiatric disorders, and that dysfunction of SAPAP scaffolding proteins may contribute to the pathogenesis of various neuropsychiatric disorders, such as schizophrenia, autism spectrum disorders, obsessive compulsive disorders, Alzheimer's disease, and bipolar disorder. Here, we review recent major genetic, epigenetic, molecular, behavioral, electrophysiological, and circuitry studies that have advanced our knowledge by clarifying the roles of SAPAP proteins at the synapses, providing new insights into the mechanistic links to neurodevelopmental and neuropsychiatric disorders.
兴奋性（谷氨酸能）突触传递是大脑活动和正常人类行为产生的基础。突触后支架蛋白 SAP90/PSD-95 相关蛋白 (SAPAPs) 是兴奋性突触后密度 (PSD) 中的丰富成分，在突触结构、形成、发育、可塑性和信号转导中发挥关键作用。人类遗传数据与最近的体外和体内动物模型数据的融合表明，编码 SAPAP1-4 的基因突变与神经和精神疾病有关，SAPAP 支架蛋白功能障碍可能导致各种神经精神疾病的发病机制，如精神分裂症、自闭症谱系障碍、强迫症、阿尔茨海默病和双相情感障碍。在这里，我们回顾了最近的主要遗传、表观遗传、分子、行为、电生理学和电路研究，这些研究通过阐明 SAPAP 蛋白在突触中的作用，为神经发育和神经精神疾病的机制联系提供了新的见解，从而提高了我们的认识。
