Cholesterol 24-Hydroxylase (CYP46A1)

A steroid hydroxylase that functions in CHOLESTEROL homeostasis in the brain. It converts cholesterol into 24S-hydroxycholesterol, which is transported over the BLOOD-BRAIN BARRIER more rapidly than unmetabolized cholesterol.

Also Known As:

CYP46A1; 5(beta)-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol-24S-hydroxylase; Brain-Specific 24S-Hydroxylase; Cholestane Tetrol 24-Hydroxylase; Cytochrome P450 46A1; Brain Specific 24S Hydroxylase; Cholestane Tetrol 24 Hydroxylase; Cholesterol 24 Hydroxylase

Networked: 104 relevant articles (6 outcomes, 19 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Pikuleva, Irina A: 13 articles (01/2022 - 02/2013)
2.	Mast, Natalia: 11 articles (01/2022 - 02/2013)
3.	Cartier, Nathalie: 7 articles (01/2021 - 01/2010)
4.	Petrov, Alexey M: 6 articles (01/2021 - 01/2019)
5.	Björkhem, Ingemar: 6 articles (12/2019 - 04/2007)
6.	Moutinho, Miguel: 5 articles (12/2016 - 01/2010)
7.	Nunes, Maria João: 5 articles (12/2016 - 01/2010)
8.	Rodrigues, Elsa: 5 articles (12/2016 - 01/2010)
9.	Acar, Niyazi: 5 articles (11/2012 - 04/2007)
10.	Bretillon, Lionel: 5 articles (11/2012 - 04/2007)

Related Diseases

1.	Alzheimer Disease (Alzheimer's Disease) 02/07/2014 - "Genetically increased CYP46A1 expression in mice leads to improved cognition and decreases manifestations of Alzheimer disease. " 08/09/2013 - "CYP46A1 intron-2T/C polymorphism and Alzheimer's disease: an updated meta-analysis of 16 studies including 3,960 cases and 3,828 controls." 07/01/2013 - "Studies of the relationship between Alzheimer's disease (AD) and single nucleotide polymorphism (SNP) T/C in intron 2 of the cholesterol-24S-hydroxylase gene (CYP46A1) have reported inconsistent results. " 07/11/2022 - "At small doses, EFV allosterically activates CYP46A1 in mice and humans and mitigates some of the Alzheimer's disease manifestations in 5XFAD mice, an animal model. " 01/01/2020 - "Modulation of CYP46A1 activity may affect Aβ deposition and p-tau accumulation by changing 24-HC formation, which thereafter serves as potential therapeutic pathway for Alzheimer's disease. "
2.	Brain Diseases (Brain Disorder) 06/15/2023 - "This article, using recent studies, highlights the role of CYP46A1 in various brain diseases and insults." 01/01/2021 - "The potential therapeutic role of CYP46A1, demonstrated in numerous models of brain disorders, is currently being evaluated in early clinical trials. " 01/01/2020 - "Cytochrome P450 46A1 is emerging as a promising therapeutic target for various brain diseases with both enzyme activation and inhibition having therapeutic potential. " 12/30/2021 - "Evidence is accumulating that modulation of CYP46A1 activity by gene therapy or pharmacologic means could be beneficial in case neurodegenerative and other brain diseases and affect brain processes other than cholesterol biosynthesis and elimination. " 01/01/2021 - "To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE). "
3.	Huntington Disease (Huntington's Disease) 03/01/2016 - "We conclude that restoring CYP46A1 activity in the striatum promises a new therapeutic approach in Huntington's disease. " 03/01/2016 - "In the R6/2 Huntington's disease mouse model, adeno-associated virus-mediated delivery of CYP46A1 into the striatum decreased neuronal atrophy, decreased the number, intensity level and size of Exp-HTT aggregates and improved motor deficits, as assessed by rotarod and clasping behavioural tests. " 04/10/2020 - "The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease." 03/01/2016 - "In vivo, in a wild-type context, knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1, reproduced the Huntington's disease phenotype, with spontaneous striatal neuron degeneration and motor deficits, as assessed by rotarod. " 01/01/2019 - "In zQ175 Huntington's disease knock-in mice, CYP46A1 prevented neuronal dysfunctions and restored cholesterol homeostasis. "
4.	Macular Degeneration (Age-Related Maculopathy) 10/09/2012 - "We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration (AMD). " 10/09/2012 - "Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in age-related macular degeneration." 01/01/2023 - "Thus, aged Cyp46a1-/- mice on high fat cholesterol-enriched diet revealed pathological changes secondary to retinal cholesterol overload and supported further studies of HPCD as a potential therapeutic for age-related macular degeneration and diabetic retinopathy associated with retinal cholesterol dyshomeostasis." 04/01/2007 - "Based on the link between cholesterol-24S-hydroxylase, 24S-hydroxycholesterol, and neurologic disorders, CYP46A1 may be a valuable gene candidate for retinal pathologies like age-related macular degeneration or glaucomas, and 24S-hydroxycholesterol may be involved in the onset of the degenerative processes in these diseases."
5.	Diabetic Retinopathy (Retinopathy, Diabetic) 01/01/2019 - "The retina of Cyp46a1-/- mice exhibited venous beading and tortuosity, microglia/macrophage activation, and increased vascular permeability, features commonly associated with diabetic retinopathy. " 01/01/2023 - "Thus, aged Cyp46a1-/- mice on high fat cholesterol-enriched diet revealed pathological changes secondary to retinal cholesterol overload and supported further studies of HPCD as a potential therapeutic for age-related macular degeneration and diabetic retinopathy associated with retinal cholesterol dyshomeostasis."

Related Drugs and Biologics

1.	Cholesterol
2.	efavirenz (Sustiva)
3.	Retinaldehyde (Retinal)
4.	Acetyl Coenzyme A (Acetyl-CoA)
5.	Cholesterol 24-Hydroxylase (CYP46A1)
6.	Enzymes
7.	24-hydroxycholesterol
8.	Cytochrome P450 Family 46 (CYP46)
9.	soticlestat
10.	Neuroprotective Agents

Related Therapies and Procedures

1.	Therapeutics