Structural highlights
Function[NPTX1_HUMAN] May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses. Publication Abstract from PubMedNeuronal 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. A synthetic synaptic organizer protein restores glutamatergic neuronal circuits.,Suzuki K, Elegheert J, Song I, Sasakura H, Senkov O, Matsuda K, Kakegawa W, Clayton AJ, Chang VT, Ferrer-Ferrer M, Miura E, Kaushik R, Ikeno M, Morioka Y, Takeuchi Y, Shimada T, Otsuka S, Stoyanov S, Watanabe M, Takeuchi K, Dityatev A, Aricescu AR, Yuzaki M Science. 2020 Aug 28;369(6507). pii: 369/6507/eabb4853. doi:, 10.1126/science.abb4853. PMID:32855309[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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