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Publication : A synthetic synaptic organizer protein restores glutamatergic neuronal circuits.

First Author  Suzuki K Year  2020
Journal  Science Volume  369
Issue  6507 PubMed ID  32855309
Mgi Jnum  J:297640 Mgi Id  MGI:6456947
Doi  10.1126/science.abb4853 Citation  Suzuki K, et al. (2020) A synthetic synaptic organizer protein restores glutamatergic neuronal circuits. Science 369(6507)
abstractText  Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.
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