2020/08/28
Japan Science and Technology Agency (JST)
Keio University
Aichi Medical University
Under the JST Strategic Basic Research Programs, a research group led by Professor Michisuke Yuzaki and Assistant Professor Kunimichi Suzuki of the Department of Physiology, Keio University School of Medicine, has succeeded for the first time in the world in developing an artificial synaptic connector that forms synapses, the junctions between neurons, and rapidly reconnects severed neural circuits.
Synapses, the junctions between neurons, are formed, maintained, and reorganized from the developmental stage throughout life by the action of synaptic organizers. The onset of many psychiatric and neurological disorders, such as autism spectrum disorder, schizophrenia, and Alzheimer's disease, is thought to be partly caused by abnormalities in the number or function of synapses, and the development of methods to correct these synaptic abnormalities has been sought.
In previous research, Professor Yuzaki's group discovered Cbln1 (Cerebellin-1), a type of synaptic organizer that acts as a synaptic connector, mainly connecting presynaptic and postsynaptic terminals in the cerebellum. This time, they elucidated the crystal structure of another synaptic organizer molecule, neuronal pentraxin (NP1), and by combining it with its structure, they developed a new artificial synaptic connector, CPTX. CPTX has the powerful property of being able to connect synapses in a wide range of neural circuits. When CPTX was administered to model mice with cerebellar ataxia, Alzheimer's disease, and spinal cord injury, all of which involve synapse loss or abnormalities, synapses were reformed within a few days. This led to significant improvements in each pathological condition, including improved motor coordination, recovery of learning and memory functions, and recovery of motor function in paralyzed hind limbs.
By applying the design principle of CPTX, it is also possible to develop new artificial synaptic connectors that can induce synaptic connections in various neural circuits. This is expected to lead to the elucidation of the mechanisms of synapse formation and maintenance, and to the creation and application of new therapeutic strategies for psychiatric and neurological disorders.
This research is the result of international collaborative research with the research groups of Professor Alexander Dityatev of the German Center for Neurodegenerative Diseases (DZNE), Professor Radu Aricescu of the MRC Laboratory of Molecular Biology in the UK, and Professor Kosei Takeuchi and Assistant Professor Hiroyuki Sasakura of Aichi Medical University.
The results of this research were published in the online edition of the American scientific journal "Science" on August 28, 2020 (US Eastern Time).
For the full press release, please see below.