Downloads provided by UsageCountsInterference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome
Copyright policy ) Mansilla A.; Chaves-Sanjuan A.; Campillo N. E.; Semelidou O.; Martinez-Gonzalez L.; Infantes L.; Gonzalez-Rubio J. M.; +6 Authors
Mansilla A.; Chaves-Sanjuan A.; Campillo N. E.; Semelidou O.; Martinez-Gonzalez L.; Infantes L.; Gonzalez-Rubio J. M.; Gil C.; Conde S.; Skoulakis E. M. C.; Ferrus A.; Martinez A.; Sanchez-Barrena M. J.;
Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome
Significance Neurons coregulate their number of synapses and the probability of neurotransmitter release per synapse in an antagonistic manner. The binding of neuronal calcium sensor 1 (NCS-1) to the guanine exchange factor protein Ric8a coregulates these neuronal features. This study identified a small molecule, the phenothiazine FD44, that binds the interaction surface between NCS-1 and Ric8a, preventing the formation of the complex. Tested on a Drosophila model of the fragile X syndrome, where the number of synapses is in excess, FD44 proves effective to reduce synapse number to normal levels and restore normal learning performance. Our structure–function study shows the specificity of this compound and the drugability of the NCS-1/Ric8a interface for the treatment of fragile X and possibly, other synaptopathies.
Italy
Models, Molecular, Neuronal Calcium-Sensor Proteins, Crystallography, X-Ray, Protein Domains, Phenothiazines, Animals, Drosophila Proteins, Guanine Nucleotide Exchange Factors, Humans, Amino Acid Sequence, fragile X syndrome, X-ray crystallography, NCS-1, Molecular Structure, Sequence Homology, Amino Acid, protein–protein interaction inhibitor, Neuropeptides, synapse regulation, Disease Models, Animal, Drosophila melanogaster, Fragile X Syndrome, Synapses, Fragile x syndrome; NCS-1; Protein-protein interaction inhibitor; Synapse regulation; X-ray crystallography; Amino Acid Sequence; Animals; Antipsychotic Agents; Crystallography, X-Ray; Disease Models, Animal; Drosophila Proteins; Drosophila melanogaster; Fragile X Syndrome; Guanine Nucleotide Exchange Factors; Humans; Models, Molecular; Molecular Structure; Neuronal Calcium-Sensor Proteins; Neuropeptides; Phenothiazines; Protein Binding; Protein Domains; Sequence Homology, Amino Acid; Synapses, Antipsychotic Agents, Protein Binding
Models, Molecular, Neuronal Calcium-Sensor Proteins, Crystallography, X-Ray, Protein Domains, Phenothiazines, Animals, Drosophila Proteins, Guanine Nucleotide Exchange Factors, Humans, Amino Acid Sequence, fragile X syndrome, X-ray crystallography, NCS-1, Molecular Structure, Sequence Homology, Amino Acid, protein–protein interaction inhibitor, Neuropeptides, synapse regulation, Disease Models, Animal, Drosophila melanogaster, Fragile X Syndrome, Synapses, Fragile x syndrome; NCS-1; Protein-protein interaction inhibitor; Synapse regulation; X-ray crystallography; Amino Acid Sequence; Animals; Antipsychotic Agents; Crystallography, X-Ray; Disease Models, Animal; Drosophila Proteins; Drosophila melanogaster; Fragile X Syndrome; Guanine Nucleotide Exchange Factors; Humans; Models, Molecular; Molecular Structure; Neuronal Calcium-Sensor Proteins; Neuropeptides; Phenothiazines; Protein Binding; Protein Domains; Sequence Homology, Amino Acid; Synapses, Antipsychotic Agents, Protein Binding
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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