| Literature DB >> 32855309 |
Kunimichi Suzuki1, Jonathan Elegheert2, Inseon Song3, Hiroyuki Sasakura4, Oleg Senkov3, Keiko Matsuda1, Wataru Kakegawa1, Amber J Clayton2, Veronica T Chang2,5, Maura Ferrer-Ferrer3, Eriko Miura1, Rahul Kaushik3,6, Masashi Ikeno4, Yuki Morioka4, Yuka Takeuchi4, Tatsuya Shimada1, Shintaro Otsuka1, Stoyan Stoyanov3, Masahiko Watanabe7, Kosei Takeuchi4, Alexander Dityatev8,6,9, A Radu Aricescu10,5, Michisuke Yuzaki11.
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.Entities:
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Year: 2020 PMID： 32855309 PMCID： PMC7116145 DOI： 10.1126/science.abb4853
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714