ReferenceID 3605
Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes
J Clin Invest
Ciliopathies are clinically overlapping genetic disorders involving structural and functional abnormalities of cilia. Currently, there are no small-molecule drugs available to treat ciliary defects in ciliopathies. Our p
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3605
- Evidence Id
- 20195
- Core Evidence Id
- 20195
- Source Reference Id
- 513
- Herb2 Reference Id
- HBREF000863
- Subject Paper Key
- HBIN026145_30035750
- Pubmed Id
- 30035750
- Doi
- 10.1172/JCI99232
- Paper Title
- Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes
- Paper Abstract
- Ciliopathies are clinically overlapping genetic disorders involving structural and functional abnormalities of cilia. Currently, there are no small-molecule drugs available to treat ciliary defects in ciliopathies. Our phenotype-based screen identified the flavonoid eupatilin and its analogs as lead compounds for developing ciliopathy medication. CEP290, a gene mutated in several ciliopathies, encodes a protein that forms a complex with NPHP5 to support the function of the ciliary transition zone. Eupatilin relieved ciliogenesis and ciliary receptor delivery defects resulting from deletion of CEP290. In rd16 mice harboring a blinding Cep290 in-frame deletion, eupatilin treatment improved both opsin transport to the photoreceptor outer segment and electrophysiological responses of the retina to light stimulation. The rescue effect was due to eupatilin-mediated inhibition of calmodulin binding to NPHP5, which promoted NPHP5 recruitment to the ciliary base. Our results suggest that deficiency of a ciliopathy protein could be mitigated by small-molecule compounds that target other ciliary components that interact with the ciliopathy protein.
- Journal
- J Clin Invest
- Publish Year
- 2018
- Experiment Subject
- rd16 mice
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes
- Bilingual Status
- semi_complete