Irina A Pikuleva
Affiliation: Case Western Reserve University
- Saadane A, Mast N, Charvet C, Omarova S, Zheng W, Huang S, et al. Retinal and nonocular abnormalities in Cyp27a1(-/-)Cyp46a1(-/-) mice with dysfunctional metabolism of cholesterol. Am J Pathol. 2014;184:2403-19 pubmed publisher..Our findings demonstrate the importance of retinal cholesterol metabolism for maintenance of the normal retina, and suggest new targets for diseases affecting the retinal vasculature. ..
- Mast N, Saadane A, Valencia Olvera A, Constans J, Maxfield E, Arakawa H, et al. Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease. Neuropharmacology. 2017;123:465-476 pubmed publisher..We suggest that CYP46A1 activation by efavirenz could be a new anti-Alzheimer's disease treatment and a tool to study and identify normal and pathological brain processes affected by cholesterol maintenance. ..
- Lam M, Mast N, Pikuleva I. Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo. Mol Pharmacol. 2018;93:101-108 pubmed publisher..We confirmed our previous finding that CYP27A1 is a druggable enzyme and found additional drugs as well as the scaffold with potential for partial CYP27A1 inhibition in humans. ..
- Mast N, Zheng W, Stout C, Pikuleva I. Antifungal Azoles: Structural Insights into Undesired Tight Binding to Cholesterol-Metabolizing CYP46A1. Mol Pharmacol. 2013;84:86-94 pubmed publisher..Therefore, structural understanding of the azole binding not only to CYPs 51 from the pathogenic species but also to different human P450s is required to deal efficiently with this challenge. ..
- Mast N, Anderson K, Lin J, Li Y, Turko I, Tatsuoka C, et al. Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum. J Biol Chem. 2017;292:4913-4924 pubmed publisher..We identified a new physiological role of CYP46A1, an important brain enzyme and cytochrome P450 that could be activated pharmacologically. ..
- Mast N, Anderson K, Johnson K, Phan T, Guengerich F, Pikuleva I. In vitro cytochrome P450 46A1 (CYP46A1) activation by neuroactive compounds. J Biol Chem. 2017;292:12934-12946 pubmed publisher..Collectively, our in vitro data, along with those from previous cell culture and in vivo studies by others, suggest that l-Glu-induced CYP46A1 activation is of physiological relevance. ..