1. A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
- Author
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A. Radu Aricescu, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Oleg Senkov, Rahul Kaushik, Kosei Takeuchi, Michisuke Yuzaki, Hiroyuki Sasakura, Stoyan Stoyanov, Alexander Dityatev, Maura Ferrer-Ferrer, Kunimichi Suzuki, Masashi Ikeno, Eriko Miura, Amber J. Clayton, Keiko Matsuda, Wataru Kakegawa, Veronica T. Chang, Masahiko Watanabe, Jonathan Elegheert, Inseon Song, Shintaro Otsuka, and Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Nervous system ,chemistry [Recombinant Proteins] ,drug effects [Synapses] ,Hippocampus ,therapy [Cerebellar Ataxia] ,Mice ,0302 clinical medicine ,Postsynaptic potential ,drug effects [Spine] ,ComputingMilieux_MISCELLANEOUS ,Multidisciplinary ,Glutamate receptor ,therapeutic use [Protein Precursors] ,genetics [Receptors, Glutamate] ,therapeutic use [Nerve Tissue Proteins] ,Motor coordination ,chemistry [Protein Precursors] ,medicine.anatomical_structure ,Excitatory postsynaptic potential ,pharmacology [Recombinant Proteins] ,Ionotropic effect ,pharmacology [C-Reactive Protein] ,Biology ,Neurotransmission ,03 medical and health sciences ,Glutamatergic ,Protein Domains ,medicine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,therapeutic use [Recombinant Proteins] ,therapy [Alzheimer Disease] ,drug effects [Neural Pathways] ,therapeutic use [C-Reactive Protein] ,metabolism [Receptors, AMPA] ,Mice, Mutant Strains ,Mice, Inbred C57BL ,pharmacology [Protein Precursors] ,Disease Models, Animal ,030104 developmental biology ,HEK293 Cells ,ddc:320 ,pharmacology [Nerve Tissue Proteins] ,chemistry [Nerve Tissue Proteins] ,Neuroscience ,030217 neurology & neurosurgery ,chemistry [C-Reactive Protein] ,physiology [Spine] - Abstract
Synthetic excitatory synaptic organizer The 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. Science , this issue p. eabb4853 ; see also p. 1052
- Published
- 2020
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