| First Author | Kim YJ | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 8 | Pages | 3642-3648 |
| PubMed ID | 30035750 | Mgi Jnum | J:265676 |
| Mgi Id | MGI:6193108 | Doi | 10.1172/JCI99232 |
| Citation | Kim YJ, et al. (2018) Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes. J Clin Invest 128(8):3642-3648 |
| abstractText | 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. |
