@article {Suzuki2020.02.27.967836, author = {Kunimichi Suzuki and Jonathan Elegheert and Inseon Song and Hiroyuki Sasakura and Oleg Senkov and Wataru Kakegawa and Amber J. Clayton and Veronica T. Chang and Maura Ferrer-Ferrer and Eriko Miura and Rahul Kaushik and Masashi Ikeno and Yuki Morioka and Yuka Takeuchi and Tatsuya Shimada and Shintaro Otsuka and Stoyan Stoyanov and Masahiko Watanabe and Kosei Takeuchi and Alexander Dityatev and A. Radu Aricescu and Michisuke Yuzaki}, title = {A synthetic synaptic organizer protein restores glutamatergic neuronal circuits}, elocation-id = {2020.02.27.967836}, year = {2020}, doi = {10.1101/2020.02.27.967836}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Neuronal synapses undergo structural and functional changes throughout life, 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 report the design and characterization of CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1 to interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors. CPTX induced the formation of excitatory synapses in vitro and in vivo and restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer{\textquoteright}s disease and spinal cord injury, respectively. Thus, CPTX represents a prototype for novel structure-guided biologics that can efficiently repair or remodel neuronal circuits.One Sentence Summary Structural biology information was used to design CPTX, a synthetic protein that induces functional excitatory synapses and restores normal behaviors in mouse models of neurological diseases.}, URL = {https://www.biorxiv.org/content/early/2020/02/27/2020.02.27.967836}, eprint = {https://www.biorxiv.org/content/early/2020/02/27/2020.02.27.967836.full.pdf}, journal = {bioRxiv} }