Results 21 to 30 of about 1,473 (145)

The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

BMC Research Notes, 2020
Objective Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim
Clévio Nóbrega, André Conceição, Rafael G. Costa, Rebekah Koppenol, Raquel L. Sequeira, Ricardo Nunes, Sara Carmo-Silva, Adriana Marcelo, Carlos A. Matos, Sandrine Betuing, Jocelyne Caboche, Nathalie Cartier, Sandro Alves   +12 more
doaj   +1 more source

Increased Plasma Level of 24S-Hydroxycholesterol and Polymorphism of CYP46A1 SNP (rs754203) Are Associated With Mild Cognitive Impairment in Patients With Type 2 Diabetes

Frontiers in Aging Neuroscience, 2021
BackgroundAbnormal cholesterol metabolism is common in type 2 diabetes mellitus (T2DM) and causes dementia. Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol (24-OHC) and maintains cholesterol homeostasis in the brain.
Jijing Shi, Jijing Shi, Jianhong Jia, Sai Tian, Sai Tian, Haoqiang Zhang, Haoqiang Zhang, Ke An, Ke An, Wenwen Zhu, Wenwen Zhu, Wuyou Cao, Wuyou Cao, Yang Yuan, Shaohua Wang   +14 more
doaj   +1 more source

Polymorphism of CYP46A1 Gene and Alzheimer’s Disease in the Iranian Population [PDF]

Shiraz E-Medical Journal, 2016
Background: Cholesterol homeostasis in the brain has been demonstrated in the pathogenesis of Alzheimer’s disease (AD). Experimental data support that brain cholesterol turnover can modulate central processes in AD pathogenesis. Excess cholesterol is eliminated from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46A1), a main ...
Rohollah Mousavidehmordi, Hossain Babaahmadi, Bita Shalbafan, Ghorban Mohammadzadeh, Mohammadreza Afsharmanesh, Alireza Kheirollah   +5 more
openaire   +1 more source

Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice

Acta Neuropathologica Communications, 2021
Prion diseases are fatal, infectious, and incurable neurodegenerative disorders caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform (PrPSc). In humans, there are sporadic, genetic and infectious etiologies, with sporadic
Tahir Ali, Samia Hannaoui, Satish Nemani, Waqas Tahir, Irina Zemlyankina, Pearl Cherry, Su Yeon Shim, Valerie Sim, Hermann M. Schaetzl, Sabine Gilch   +9 more
doaj   +1 more source

2-Hydroxypropyl-β-cyclodextrin mitigates pathological changes in a mouse model of retinal cholesterol dyshomeostasis

Journal of Lipid Research, 2023
CYP46A1 is a CNS-specific enzyme, which eliminates cholesterol from the brain and retina by metabolism to 24-hydroxycholesterol, thus contributing to cholesterol homeostasis in both organs.
Nicole El-Darzi, Natalia Mast, Sandra S. Hammer, Tim F. Dorweiler, Julia V. Busik, Irina A. Pikuleva   +5 more
doaj   +1 more source

The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase in vitro and in vivo

Journal of Lipid Research, 2010
Cholesterol 24S-hydroxylase (CYP46A1) is of key importance for cholesterol homeostasis in the brain. This enzyme seems to be resistant toward most regulatory factors and at present no drug effects on its activity have been described.
Marjan Shafaati, Natalia Mast, Olof Beck, Rima Nayef, Gun Young Heo, Linda Björkhem-Bergman, Dieter Lütjohann, Ingemar Björkhem, Irina A. Pikuleva   +8 more
doaj   +1 more source

CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer’s disease

Alzheimer’s Research & Therapy, 2022
Background Efavirenz is an anti-HIV drug, and cytochrome P450 46A1 (CYP46A1) is a CNS-specific enzyme that metabolizes cholesterol to 24-hydroxycholesterol (24HC).
Alan J. Lerner, Steven E. Arnold, Erin Maxfield, Aaron Koenig, Maria E. Toth, Brooke Fortin, Natalia Mast, Bianca A. Trombetta, John Denker, Andrew A. Pieper, Curtis Tatsuoka, Sangeetha Raghupathy, Irina A. Pikuleva   +12 more
doaj   +1 more source

In Vitro Activation of Cytochrome P450 46A1 (CYP46A1) by Efavirenz-Related Compounds [PDF]

Journal of Medicinal Chemistry, 2019
Cytochrome P450 46A1 (CYP46A1) is a central nervous system-specific enzyme, which catalyzes cholesterol 24-hydroxylation. Currently CYP46A1 is being evaluated in a clinical trial for activation by small doses of the anti-HIV drug efavirenz. Eight efavirenz-related compounds were investigated for CYP46A1 activation in vitro, induction of a CYP46A1 ...
Natalia Mast, Peter Verwilst, Clayton J. Wilkey, F. Peter Guengerich, Irina A. Pikuleva   +4 more
openaire   +2 more sources

Targeting cytochrome P450 46A1 and brain cholesterol 24-hydroxylation to treat neurodegenerative diseases

Exploration of Neuroprotective Therapy, 2021
The brain cholesterol content is determined by the balance between the pathways of in situ biosynthesis and cholesterol elimination via 24-hydroxylation catalyzed by cytochrome P450 46A1 (CYP46A1). Both pathways are tightly coupled and determine the rate
Irina A. Pikuleva
doaj   +1 more source

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

Frontiers in Pharmacology, 2022
A small dose of the anti-HIV drug efavirenz (EFV) was previously discovered to activate CYP46A1, a cholesterol-eliminating enzyme in the brain, and mitigate some of the manifestation of Alzheimer’s disease in 5XFAD mice.
Nicole El-Darzi, Natalia Mast, David A. Buchner, Aicha Saadane, Brian Dailey, Georgios Trichonas, Irina A. Pikuleva   +6 more
doaj   +1 more source