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Synthetic excitatory synaptic organizer - Science, August 2020

Synthetic excitatory synaptic organizer - Science, August 2020

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

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.

Cartoon illustrating how CPTX works by forming a molecular bridge between pre- and post-synaptic neurons.

Authors: Kunimichi Suzuki, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Keiko Matsuda, Wataru Kakegawa, Amber J. Clayton, Veronica T. Chang, Maura Ferrer-Ferrer, Eriko Miura, Rahul Kaushik, Masashi Ikeno, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Shintaro Otsuka, Stoyan Stoyanov, Masahiko Watanabe, Kosei Takeuchi, Alexander Dityatev, A. Radu Aricescu, Michisuke Yuzaki

- Science, 28 Aug 2020: Vol. 369, Issue 6507, eabb4853 - DOI: 10.1126/science.abb4853
- Contact: Jonathan Elegheert