Yokohama City University Graduate School of Medicine, Department of Physiology.
Keio University School of Medicine, Department of Neuropsychiatry.
Proc Jpn Acad Ser B Phys Biol Sci. 2021;97(1):1-21. doi: 10.2183/pjab.97.001.
Psychiatric and neurological disorders severely hamper patient's quality of life. Despite their high unmet needs, the development of diagnostics and therapeutics has only made slow progress. This is due to limited evidence on the biological basis of these disorders in humans. Synapses are essential structural units of neurotransmission, and neuropsychiatric disorders are considered as "synapse diseases". Thus, a translational approach with synaptic physiology is crucial to tackle these disorders. Among a variety of synapses, excitatory glutamatergic synapses play central roles in neuronal functions. The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a principal component of glutamatergic neurotransmission; therefore, it is considered to be a promising translational target. Here, we review the limitations of current diagnostics and therapeutics of neuropsychiatric disorders and advocate the urgent need for the promotion of translational medicine based on the synaptic physiology of AMPAR. Furthermore, we introduce our recent translational approach to these disorders by targeting at AMPARs.
精神和神经紊乱严重影响了患者的生活质量。尽管这些疾病存在巨大的未满足的需求,但在诊断和治疗方面的进展却非常缓慢。这是因为人类对于这些疾病的生物学基础的了解非常有限。突触是神经传递的基本结构单位,神经精神疾病被认为是“突触疾病”。因此,采用突触生理学的转化方法对于治疗这些疾病至关重要。在各种突触中,兴奋性谷氨酸能突触在神经元功能中起着核心作用。谷氨酸 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)是谷氨酸能神经传递的主要组成部分;因此,它被认为是一个很有前途的转化治疗靶点。在这里,我们回顾了目前神经精神疾病的诊断和治疗的局限性,并提倡迫切需要基于 AMPAR 的突触生理学来促进转化医学。此外,我们还介绍了我们最近针对 AMPAR 靶向治疗这些疾病的转化方法。