Snippet: Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.
Affiliation: 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. BGI-Shenzhen, Shenzhen 518083, China. 1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] CapitalBio Genomics Co., Ltd., Dongguan 523808, China. 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA. Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. Department of Biochemistry, University of California Riverside, Riverside, California 92521, USA. 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA. King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [4] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA. .
2: Title: Design and evaluation of a novel series of 2,3-oxidosqualene cyclase inhibitors with low systemic exposure, relationship between pharmacokinetic properties and ocular toxicity.
Snippet: We describe the discovery of novel potent inhibitors of 2,3-oxidosqualene:lanosterol cyclase inhibitors (OSCi) from a focused pharmacophore-based screen.
Affiliation: Department of Medicinal chemistry, Laboratoire GlaxoSmithKline, 25-27 Avenue du Québec, 91951 LesUlis, France. marie-helene.fouchet@gsk.com .
Snippet: Hypomorphic mutations were identified in genes for lanosterol synthase (Lss) on chromosome 20 and farnesyldiphosphatefarnesyltransferase 1 (Fdft1) on chromosome 15, both of which function in the cholesterolbiosynthesis pathway.
Affiliation: Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan. masamori@sch.md.shinshu-u.ac.jp .
Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie (Exp Toxicol Pathol), Vol. 57 (1): 29-38, 2005 .
Snippet: In dogs, the agents produced equatorial single cell necrosis and cataract in the lens (also observed clinically); atrophy, ulceration, and inflammation of the cornea; hyperkeratosis, acanthosis, hair papillary atrophy, and inflammation of the skin; and epithelial degeneration and spermgranuloma in the epididymides.
