Department of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan 00931, Puerto Rico.
Clinical Bioreagent Center, Molecular Sciences Research Center, University of Puerto Rico, San Juan 00926, Puerto Rico.
Molecules. 2021 Sep 23;26(19):5753. doi: 10.3390/molecules26195753.
Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neurodegenerative disorders. Nevertheless, their therapeutic value has been limited by the absence of high-resolution structures that allow for the design of more specific and effective drugs. This article offers a comprehensive review of five decades of research pursuing high-resolution structures of nAChRs. We provide a historical perspective, from initial structural studies to the most recent X-ray and cryogenic electron microscopy (Cryo-EM) nAChR structures. We also discuss the most relevant structural features that emerged from these studies, as well as perspectives in the field.
自发现以来，烟碱型乙酰胆碱受体（nAChRs）一直是研究的热点，旨在了解其功能，以及导致疾病状态的改变的后果。重要的是，这些受体是治疗多种神经和神经退行性疾病的药理学靶点。然而，由于缺乏高分辨率结构，使得设计更具特异性和更有效的药物受到限制，因此它们的治疗价值受到限制。本文全面回顾了五十年以来追求 nAChRs 高分辨率结构的研究。我们提供了从最初的结构研究到最近的 X 射线和低温电子显微镜（Cryo-EM）nAChR 结构的历史视角。我们还讨论了这些研究中出现的最相关的结构特征，以及该领域的展望。
