A New Synthetic Molecule Repairs Damage to the Brain and Spinal Cord －A Bridge over Troubled Synapses in Neuropsychiatric and Neurological Disorders－
Oct. 16, 2020
Japan Science and Technology Agency (JST) Keio University
Aichi Medical University
Through a JST Strategic Basic Research Program, a research team led by Professor Michisuke Yuzaki and Assistant Professor Kunimichi Suzuki of the Department of Physiology, Keio University School of Medicine, have developed a novel synthetic synaptic organizer that can quickly connect a neural circuit.
Synapses, which are the connections between nerve cells, are formed, maintained, and remodeled not only during organism development, but also throughout life by synaptic organizers. The onset of many neuropsychiatric or neurological disorders, such as autism spectrum disorders, schizophrenia, and Alzheimer's disease, is considered to be due in part to an imbalance of excitatory and inhibitory synaptic signaling. However, there are currently no therapeutic methods for directly controlling the synaptic structure.
In a previous study, Professor Yuzaki's research team discovered a synaptic connector, cerebellin (Cbln1), which is a type of synaptic organizer that mainly connects pre- and postsynaptic membrane proteins in the cerebellum. Here, the team has developed a new synthetic synaptic connector, CPTX, by combining structural elements from Cbln1 and another synaptic organizer protein, neuronal pentraxin-1 (NP1). Application of CPTX to mouse models of cerebellar ataxia, Alzheimer's disease, and spinal cord injury could successfully restore synapses and improve motor coordination, spatial and contextual memories, and locomotion associated with each of these disease models, respectively.
Structure-guided design of synthetic synaptic organizers targeting distinct pre- and postsynaptic molecules may inspire the development of a variety of innovative molecular tools that can repair or remodel a wide range of neural circuits. These tools are expected to lead to the elucidation of the mechanism of synapse formation and maintenance as well as the development and application of new therapeutic treatments for neuropsychiatric or neurological disorders.
This research is the result of an international collaboration between Keio University and research teams led by Professor Alexander Dityatev of the German Center for Neurodegenerative Diseases (DZNE), Professor Radu Aricescu of the MRC Laboratory of Molecular Biology, UK, and Professor Kosei Takeuchi and Assistant Professor Hiroyuki Sasakura of Aichi Medical University.
The results of this research were published online on August 28, 2020 (EST), in the American scientific journal Science.
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