A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
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DOI：
10.1126/science.abb4853
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发表时间：
2020-08-28
期刊：
影响因子：
56.9
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
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作者：
Suzuki, Kunimichi;Elegheert, Jonathan;Yuzaki, Michisuke
神经元突触在整个生命过程中经历结构和功能变化，这对神经系统生理学至关重要。然而，这些变化也可能扰乱兴奋-抑制神经传递平衡，并引发神经精神和神经系统疾病。恢复这种平衡的分子工具是非常可取的。在这里，我们设计和特点CPTX，一种合成的突触组织者结合结构元素从小脑蛋白-1和神经元pentraxin-1。CPTX可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，并诱导兴奋性突触的形成。CPTX分别恢复了小脑共济失调、阿尔茨海默病和脊髓损伤小鼠模型的突触功能、运动协调、空间和背景记忆以及运动。因此，CPTX代表了结构引导生物制剂的原型，可以有效地修复或重塑神经元回路。
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.