Zhu Hongtao
Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.
Front Pharmacol. 2022 Aug 9;13:925116. doi: 10.3389/fphar.2022.925116. eCollection 2022.
Glycine receptors (GlyRs) are pentameric ion channels that mediate fast inhibitory neurotransmission. GlyRs are found in the central nervous system including the spinal cord, brain stem, and cerebellum, as well as in the retina, sperm, macrophages, hippocampus, cochlea, and liver. Due to their crucial roles in counter-balancing excitatory signals and pain signal transmission, GlyR dysfunction can lead to severe diseases, and as a result, compounds that modify GlyR activity may have tremendous therapeutic potential. Despite this potential, the development of GlyR-specific small-molecule ligands is lacking. Over the past few years, high-resolution structures of both homomeric and heteromeric GlyRs structures in various conformations have provided unprecedented details defining the pharmacology of ligand binding, subunit composition, and mechanisms of channel gating. These high-quality structures will undoubtedly help with the development of GlyR-targeted therapies.
甘氨酸受体（GlyRs）是介导快速抑制性神经传递的五聚体离子通道。甘氨酸受体存在于中枢神经系统，包括脊髓、脑干和小脑，以及视网膜、精子、巨噬细胞、海马体、耳蜗和肝脏中。由于它们在平衡兴奋性信号和疼痛信号传递中起关键作用，甘氨酸受体功能障碍可导致严重疾病，因此，调节甘氨酸受体活性的化合物可能具有巨大的治疗潜力。尽管有这种潜力，但缺乏针对甘氨酸受体的小分子配体的开发。在过去几年中，各种构象的同聚体和异聚体甘氨酸受体的高分辨率结构提供了前所未有的细节，这些细节定义了配体结合的药理学、亚基组成和通道门控机制。这些高质量的结构无疑将有助于开发针对甘氨酸受体的疗法。
