Compound library screening for identification of ciliopathy therapeutics = 화합물 스크리닝을 이용한 Ciliopathy 치료전략 개발

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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. My phenotype-based screen identified a flavonoid eupatilin and its analogs as lead compounds for developing ciliopathy medication. CEP290, a gene mutated in several ciliopathies, encodes a protein that complexes 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 the 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. My 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.
Advisors
Kim, Joonresearcher김준researcher
Description
한국과학기술원 :의과학대학원,
Publisher
한국과학기술원
Issue Date
2019
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 의과학대학원, 2019.2,[iv, 63 p. :]

Keywords

Ciliopathy▼aphotoreceptor▼aeupatilin▼aCEP290▼aNPHP5; 섬모병증▼a광수용체▼aEupatilin▼aCEP290▼aNPHP5

URI
http://hdl.handle.net/10203/265087
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=842188&flag=dissertation
Appears in Collection
MSE-Theses_Ph.D.(박사논문)
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