De Los Reyes Dominique Alexandra, Karkoutly Mohammad Yaman, Zhang Yonghong
School of Integrative Biological and Chemical Sciences, The University of Texas Rio Grande Valley, Edinburg, TX, United States.
Front Mol Neurosci. 2023 Oct 19;16:1286134. doi: 10.3389/fnmol.2023.1286134. eCollection 2023.
Neurodevelopmental and neurodegenerative disorders are primarily characterized by serious structural and functional changes in excitatory glutamatergic synapses in the brain, resulting in many synaptic deficits and aberrant synapse loss. It is a big challenge to reverse these synaptic impairments as a treatment for neurological diseases in the field. Extensive research on glutamate receptors as therapeutic targets has been done but with little success shown in human trials. PSD-95-like MAGUK proteins perform a pivotal role in regulating the trafficking and stability of glutamate receptors that are important to postsynaptic structure and function. MAGUK and MAGUK-modulated synaptic pathways are becoming promising candidates for developing therapeutic targets. As a MAGUK protein, SAP102 is not understood well compared to PSD-95. Here, we review the current research on SAP102 including its synaptic functions and regulation, especially its expression and functions in the early stage of synaptogenesis and the association with neurodevelopmental disorders. This review presents valuable information for future structural and functional studies of SAP102 to reveal its roles in young and mature neurons. It provides clues for developing potential remedies to reverse synaptic impairments and strategies to grow new neurons.
神经发育障碍和神经退行性疾病的主要特征是大脑中兴奋性谷氨酸能突触出现严重的结构和功能变化,导致许多突触缺陷和异常的突触丧失。作为该领域治疗神经疾病的方法,扭转这些突触损伤是一项巨大的挑战。针对谷氨酸受体作为治疗靶点已经开展了广泛研究,但在人体试验中成效甚微。类 PSD-95 的膜相关鸟苷酸激酶(MAGUK)蛋白在调节谷氨酸受体的转运和稳定性方面发挥着关键作用,而谷氨酸受体对突触后结构和功能至关重要。MAGUK 以及 MAGUK 调节的突触通路正成为开发治疗靶点的有前景的候选对象。作为一种 MAGUK 蛋白,与 PSD-95 相比,突触相关蛋白 102(SAP102)尚未得到充分了解。在此,我们综述了目前关于 SAP102 的研究,包括其突触功能和调节,特别是其在突触发生早期的表达和功能以及与神经发育障碍的关联。这篇综述为未来对 SAP102 进行结构和功能研究以揭示其在年轻和成熟神经元中的作用提供了有价值的信息。它为开发逆转突触损伤的潜在疗法以及培育新神经元的策略提供了线索。