desmosterol has been researched along with Cataract* in 3 studies
3 other study(ies) available for desmosterol and Cataract
Article | Year |
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E2012-induced cataract and its predictive biomarkers.
E2012, a gamma secretase modulator without affecting Notch processing, aimed at Alzheimer's disease by reduction of amyloid β-42, induced cataract following repeated doses in the rat. Cataract appeared first at week 10-11 of treatment as a posterior subcapsular area with granular/punctate opaque or shiny dots along the suture line, characterized histologically as lenticular fiber degeneration, which eventually coalesced to form a triangular or circular opacity. It was associated with prolonged and sustained elevation of lenticular desmosterol (24-dehydrocholesterol), the final precursor of cholesterol, and decrease in lenticular cholesterol. In vitro studies to investigate the effect of E2012 on cholesterol metabolism demonstrated that E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. In vivo lenticular concentration of E2012 after 13-week repeated dose with cataract was well above those where inhibition was observed in vitro. There was no cataract formation at doses where desmosterol did not accumulate in the lens. The elevation of desmosterol and decreased cholesterol levels were also seen in the liver and plasma and preceded those in the lens. These results demonstrate that E2012 induces cataract in the rat by inhibiting DHCR24 at the final step of cholesterol synthesis with associated elevation in desmosterol within the lens, preceded by desmosterol changes that would serve as a predictive safety biomarker for lenticular opacity. Topics: Amyloid Precursor Protein Secretases; Animals; Biomarkers; Cataract; Cholesterol; Desmosterol; Dose-Response Relationship, Drug; Female; Hep G2 Cells; Hepatocytes; Humans; Imidazoles; Lens, Crystalline; Male; Nerve Tissue Proteins; Oxidoreductases Acting on CH-CH Group Donors; Piperidines; Protease Inhibitors; Rats; Rats, Sprague-Dawley; Time Factors | 2014 |
Mechanism of cataract production by 3-beta(2-diethylaminoethoxy) androst-5-en-17-one hydrochloride, U18666A: an inhibitor of cholesterol biosynthesis.
Topics: Aging; Androstenes; Animals; Anticholesteremic Agents; Cataract; Cholesterol; Crystallins; Desmosterol; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Female; Lens, Crystalline; Male; Potassium; Rats; Sodium | 1979 |
Myotonia induced by diazacholesterol: increased (Na+ + K+)-ATPase activity of erythrocyte ghosts and development of cataracts.
Topics: Adenosine Triphosphatases; Animals; Aza Compounds; Cataract; Cell Membrane; Cholesterol; Chromatography, Gas; Desmosterol; Erythrocytes; Lipids; Magnesium; Male; Myotonia; Ouabain; Phospholipids; Potassium; Rats; Sodium | 1973 |