https://science.sciencemag.org/content/369/6507/eabb4853
RESEARCH ARTICLE A synthetic synaptic organizer protein restores glutamatergic neuronal circuits - View ORCID ProfileKunimichi Suzuki1,*,¢Ó,
- Jonathan Elegheert2,¢Ó,¢Ô,
- View ORCID ProfileInseon Song3,¢Ó,
- View ORCID ProfileHiroyuki Sasakura4,¢Ó,
- View ORCID ProfileOleg Senkov3,
- View ORCID ProfileKeiko Matsuda1,
- View ORCID ProfileWataru Kakegawa1,
- View ORCID ProfileAmber J. Clayton2,¡×,
- View ORCID ProfileVeronica T. Chang2,5,
- Maura Ferrer-Ferrer3,
- Eriko Miura1,
- View ORCID ProfileRahul Kaushik3,6,
- View ORCID ProfileMasashi Ikeno4,
- Yuki Morioka4,
- View ORCID ProfileYuka Takeuchi4,
- View ORCID ProfileTatsuya Shimada1,
- Shintaro Otsuka1,
- View ORCID ProfileStoyan Stoyanov3,
- View ORCID ProfileMasahiko Watanabe7,
- View ORCID ProfileKosei Takeuchi4,
- View ORCID ProfileAlexander Dityatev3,6,8,||,
- View ORCID ProfileA. Radu Aricescu2,5,||,
- View ORCID ProfileMichisuke Yuzaki1,||
See all authors and affiliations Science 28 Aug 2020: Vol. 369, Issue 6507, eabb4853 DOI: 10.1126/science.abb4853 Synthetic excitatory synaptic organizerThe human brain contains trillions of synapses within a vast network of neurons. Synapse remodeling is essential to ensure the efficient reception and integration of external stimuli and to store and retrieve information. Building and remodeling of synapses occurs throughout life under the control of synaptic organizer proteins. Errors in this process can lead to neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements of natural synaptic organizers to develop an artificial version called CPTX, which has different binding properties (see the Perspective by Salinas). CPTX could act as a molecular bridge to reconnect neurons and restore excitatory synaptic function in animal models of cerebellar ataxia, familial Alzheimer's disease, and spinal cord injury. The findings illustrate how structure-guided approaches can help to repair neuronal circuits.
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