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用于阐明神经元和突触连接的分子与发育生物学的神经毒素衍生光学探针:用于神经成像的毒素衍生光学探针。

Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections : Toxin-Derived Optical Probes for Neuroimaging.

作者信息

Bijjam Rohini, Shorter Susan, Bratt Alison M, O'Leary Valerie B, Ntziachristos Vasilis, Ovsepian Saak Victor

机构信息

Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Kent, ME4 4TB, UK.

Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, 10000, Prague, Czech Republic.

出版信息

Mol Imaging Biol. 2024 Dec;26(6):912-925. doi: 10.1007/s11307-024-01954-6. Epub 2024 Sep 30.

Abstract

Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neurotransmitter release at presynaptic terminals have attracted much interest in experimental neurobiology and clinical research. Fused with reporter proteins or labelled with fluorophores, BoNTs and TeTX and their non-toxic fragments also offer remarkable opportunities to visualize cellular processes and functions in neurons and synaptic connections. This study presents the state-of-the-art optical probes derived from BoNTs and TeTX and discusses their applications in molecular and synaptic biology and neurodevelopmental research. It reviews the principles of the design and production of probes, revisits their applications with advantages and limitations and considers prospects for future improvements. The versatile characteristics of discussed probes and reporters make them an integral part of the expanding toolkit for molecular neuroimaging, promoting the discovery process in neurobiology and translational neurosciences.

摘要

肉毒杆菌神经毒素(BoNTs)和破伤风毒素(TeTX)是分别导致肉毒中毒和破伤风的最致命生物物质。它们惊人的毒性以及进入神经元并干扰突触前终端神经递质释放的能力,在实验神经生物学和临床研究中引起了极大关注。与报告蛋白融合或用荧光团标记后,BoNTs、TeTX及其无毒片段也为可视化神经元中的细胞过程和功能以及突触连接提供了绝佳机会。本研究介绍了源自BoNTs和TeTX的最先进光学探针,并讨论了它们在分子和突触生物学以及神经发育研究中的应用。它回顾了探针设计和生产的原理,重新审视了它们的应用,包括优点和局限性,并考虑了未来改进的前景。所讨论的探针和报告分子的多功能特性使它们成为不断扩展的分子神经成像工具包中不可或缺的一部分,推动了神经生物学和转化神经科学的发现进程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6413/11634926/88ed57d379b5/11307_2024_1954_Fig1_HTML.jpg

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