A New Tool for Restoring Disrupted Neuronal Circuits
Thursday, January 27, 2022
5:00 PM-6:30 PM
BIOMED Special Topics: Neuroengineering Seminar Series
Title:
A New Tool for Restoring Disrupted Neuronal Circuits
Speaker:
Kunimichi Suzuki, PhD
Investigator Scientist
Radu Aricescu Laboratory
Neurobiology Division
Medical Research Council-Laboratory of Molecular Biology (MRC-LMB)
United Kingdom
Details:
Synapses, the specialized connection between two neurons, are formed, maintained and reconstructed from developmental stage throughout life and synaptic organizers play critical roles for these function by connecting between the pre/post-synaptic terminals and transduce the signaling. Since the defects in the synapses would cause many neuropsychiatric and neurological disorders, such as autism spectrum disorders, schizophrenia and Alzheimer’s diseases, it has been desired to develop a tool to restore the synaptic deficits.
In the previous study, we analyzed the structure of endogenous synaptic organizers, Cbln1 and neuronal pentraxin 1 (NP1) and carried out a rational structure-guided design to develop a new synthetic synaptic organizer, CPTX, combining the features of Cbln1 and NP1. CPTX has a strong ability to connect excitatory synapses by binding presynaptic neurexins (Nrxs) and postsynaptic AMPA type glutamate receptors (AMPARs).
Experiments in vitro and in vivo showed that CPTX induced excitatory synapse formation through Nrxs-CPTX-AMPARs complex and recovered the motor and memory function in several disease models such as cerebellar ataxia, Alzheimer’s disease and spinal cord injury by restoring the disrupted neuronal circuits. A new concept to connect the synaptic molecules by applying an artificial synapse connector based on the structural information of synaptic organizer molecules suggests a possible new approach, “the reconnection of neuronal circuits” as therapeutic method for neuropsychiatric and neurological disorders.
Biosketch:
Kunimichi Suzuki, PhD, is an Investigator Scientist at the Radu Aricescu Laboratory in the Neurobiology division of the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in the United Kingdom. Dr. Suzuki graduated from the University of Tokyo and trained at the Keio University School of Medicine as a postdoctral fellow. He works on research regarding the synapse organizing molecules, such as neurexins, cerebellins, and neuroligins, to elucidate their regulatory mechanism mediated by the proteolytic cleavage and to develop structure-guided artificial synapse organizers as therapeutic tools to restore synapses in the disease model mouse.
Contact Information
Catherine von Reyn
crv33@drexel.edu