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人工蛋白有望重塑神经突触

文章来源: 更新时间:2020-08-31 19:46

本期文章:《科学》:Volume 369 Issue 6507

日本庆应义塾大学医学院Michisuke Yuzaki等研究人员合作开发出一种合成的突触组织蛋白,可恢复谷氨酸能神经元回路。相关论文于2020年8月28日发表在《科学》杂志上。

研究人员设计并表征了CPTX,一种结合了小脑肽1和神经元穿透素1结构元件的合成突触组织因子。CPTX可以与突触前神经毒素和突触后AMPA型离子型谷氨酸受体相互作用,并在体内和体外诱导兴奋性突触的形成。CPTX分别在小脑性共济失调、阿尔茨海默氏病和脊髓损伤的小鼠模型中恢复了突触功能、运动协调、空间和背景记忆以及运动。因此,CPTX是一种结构导向生物制剂的原型,可以有效地修复或重塑神经元回路。

 

据了解,神经元突触在整个生命过程中都会经历结构和功能的变化,这对于神经系统生理至关重要。但是,这些变化也可能扰乱兴奋性抑制性神经传递平衡,并引发神经精神病和神经系统疾病。因此,能够恢复这种平衡的分子工具是非常需要的。 

 

附:英文原文

Title: A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

Author: Kunimichi Suzuki, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Keiko Matsuda, Wataru Kakegawa, Amber J. Clayton, Veronica T. Chang, Maura Ferrer-Ferrer, Eriko Miura, Rahul Kaushik, Masashi Ikeno, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Shintaro Otsuka, Stoyan Stoyanov, Masahiko Watanabe, Kosei Takeuchi, Alexander Dityatev, A. Radu Aricescu, Michisuke Yuzaki

Issue&Volume: 2020/08/28

Abstract: Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory–inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer’s disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.

DOI: 10.1126/science.abb4853

Source: https://science.sciencemag.org/content/369/6507/eabb4853

期刊信息

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037

官方网址:https://www.sciencemag.org/

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