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The structural and functional integrity of synapses is crucial for neuronal circuit function and for the ability of animals to respond and adapt to their environment. However, synapses become dysfunctional or are lost in developmental and neurodegenerative disorders, and after brain and spinal cord injury (SCI). Deficiency in synapse integrity contributes to cognitive impairment and motor disability. To restore damaged neuronal circuits after SCI, antibody therapy against molecules such as Nogo, which inhibits axon growth, are in clinical trials (1). For other conditions such as Alzheimer’s disease (AD), blockade of the pathogenic molecule amyloid-β or its downstream effects are being tested as potential therapies (2). To develop effective approaches for restoring impaired synapses, careful consideration should be given to the diversity of synaptogenic factors. To overcome this, on page 1074 of this issue, Suzuki et al. (3) report a structurally guided synthetic peptide to restore synaptic integrity of damaged and impaired circuits in mice.
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