gene

CYP46A1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about CYP46A1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

850Connections

4Hypotheses

2Analyses

50Outgoing

50Incoming

Summary

Cholesterol 24-hydroxylase (CYP46A1) is the rate-limiting enzyme for brain cholesterol turnover, converting cholesterol to 24S-hydroxycholesterol. Enhances cholesterol efflux and modulates synaptic plasticity. Gene therapy and pharmacological upregulation improve cognition in AD models by reducing amyloid burden.

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🧬 Gene Info

Gene Symbol	CYP46A1
Full Name	Cholesterol 24-Hydroxylase
Aliases	CH24H
Chromosome	14
Protein Type	Enzyme
Target Class	Enzyme
Function	CYP46A1 plays a critical role in cholesterol metabolism, which is intimately connected to Alzheimer's disease pathogenesis through multiple mechanisms:
Mechanism of Action	Small molecule activator of cholesterol 24-hydroxylase enhancing brain cholesterol turnover
Primary Expression	neurons of the brain that catalyzes the conversion of cholesterol to 24-hydroxycholesterol
Druggability	Medium (0.51)
Clinical Stage	Approved
Pathways	Cholesterol metabolism, Oxysterol synthesis, BBB transport
UniProt ID	G3V366
Ensembl ID	ENSG00000146386
GeneCards	CYP46A1
Human Protein Atlas	CYP46A1
Associated Diseases	ALS, Alzheimer, Alzheimer'S Disease, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	EFAVIRENZ, efavirenz, spermidine, efavirenz metabolites, lycibarbarspermidines D, neurotransmitters
Interactions	BDNF, APP, ABCA1, APOC1, APOC2, SOAT1
SciDEX Target	View Target Profile (6 clinical trials)
SciDEX Hypotheses	CYP46A1 Overexpression Gene Therapy TREM2-Mediated Cholesterol Dysregulation in Microg CYP46A1 Gene Therapy for Age-Related TREM2-Mediate (+1 more)
KG Connections	850 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure: CYP46A1 — PDB 2Q9F Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

CYP46A1 — Cholesterol 24-Hydroxylase

gene · 613 words

→

AAV Gene Therapy for Neurodevelopmental Epilepsy — Competitive Landscape & Delivery Alternatives

therapeutic · 15567 words

→

Pathway Diagram

graph TD
    CYP46A1["CYP46A1 Enzyme"] -->|"Hydroxylates"| Chol["Cholesterol"]
    Chol -->|"Converts to"| 24HC["24-Hydroxycholesterol"]
    24HC -->|"Crosses"| BBB["Blood-Brain Barrier"]
    24HC -->|"Exits to"| Blood["Bloodstream"]
    CYP46A1 -->|"Regulates"| Homeostasis["Brain Cholesterol Homeostasis"]
    Dysregulation -.Causes.-> Excess["Cholesterol Excess"]
    Excess -.Associated with.-> AD["Alzheimer's Disease"]
    CYP46A1 -.Upregulation therapeutic.-> Clearance["Enhanced Clearance"]

Outgoing (569)

Target	Relation	Type	Str
Cholesterol Homeostasis	regulates	process	0.95
Brain Cholesterol Accumulation	inhibits	phenotype	0.95
Cholesterol Accumulation	downregulates	phenotype	0.95
brain diseases	benefits_for	disease	0.90
lipid metabolism	participates_in	pathway	0.90
neurons	expressed_in	cell_type	0.90
GLIOBLASTOMA	downregulates	disease	0.90
Alzheimer'S Disease	risk_factor_for	disease	0.90
NEURON	expressed_in	cell_type	0.85
APOE4	interacts_with	protein	0.80
Niemann-Pick type C disease	implicated_in	disease	0.80
Amyloid-β	regulates	protein	0.80
APOE ε4 allele	interacts_with	gene	0.80
cell proliferation	inhibits	process	0.80
Alzheimer's disease	increases_risk	disease	0.80
neurons	associated_with	cell_type	0.80
Alzheimer's disease	regulates	disease	0.80
Alzheimer's disease	treats	disease	0.80
neurons	activates	cell_type	0.80
oxidative stress response	participates_in	pathway	0.80
Alzheimer's disease	biomarker_for	disease	0.80
GLAUCOMA	implicated_in	disease	0.80
"middle temporal gyrus"_spiny_L3	expressed_in	cell_type	0.70
"middle temporal gyrus"_aspiny_L3	expressed_in	cell_type	0.70
"middle temporal gyrus"_spiny_L5	expressed_in	cell_type	0.70
neurodegeneration	inhibits	disease	0.70
neurodegeneration	treats	disease	0.70
neurodegeneration	targets	disease	0.70
BACE1	destabilizes	gene	0.70
neurodegeneration	accumulates_in	disease	0.70
Alzheimer's disease	inhibits	disease	0.70
blood-brain barrier	expressed_in	brain_region	0.70
Huntington's disease	treats	disease	0.70
neurons	treats	cell_type	0.70
neurons	inhibits	cell_type	0.70
blood-brain barrier	participates_in	pathway	0.70
HUNTINGTON	implicated_in	disease	0.70
Huntington's disease	implicated_in	disease	0.70
EPILEPSY	implicated_in	disease	0.70
DEPRESSION	implicated_in	disease	0.70
COGNITIVE DECLINE	exacerbates	phenotype	0.70
WHITE MATTER	activates	brain_region	0.70
NRF2 PATHWAY	inhibits	pathway	0.70
NRF2 PATHWAY	regulates	pathway	0.70
HIPPOCAMPUS	causes	brain_region	0.70
HIPPOCAMPUS	exacerbates	brain_region	0.70
NEUROINFLAMMATION	inhibits	phenotype	0.70
NEURONS	exacerbates	cell_type	0.70
COGNITIVE DECLINE	protects_against	phenotype	0.70
AMYLOID	protects_against	protein	0.70

Incoming (281)

Source	Relation	Type	Str
ATAD3A	inhibits	gene	0.90
lycibarbarspermidines D	inhibits	compound	0.90
h-2600483e	targets_gene	hypothesis	0.90
h-var-e0e82ff2e2	targets_gene	hypothesis	0.90
h-var-1dc420e7d8	targets_gene	hypothesis	0.90
h-var-3fbcfc0e6c	targets_gene	hypothesis	0.90
h-2600483e	targets	hypothesis	0.80
efavirenz metabolites	activates	compound	0.80
APOE	co_mentioned_with	gene	0.80
neurotransmitters	activates	compound	0.70
ADAM10	inhibits	gene	0.70
ABCA1	co_mentioned_with	gene	0.70
SYNAPTIC PLASTICITY	stabilizes	phenotype	0.70
SYNAPTIC PLASTICITY	treats	phenotype	0.70
SYNAPTIC PLASTICITY	protects_against	phenotype	0.70
SYNAPTIC PLASTICITY	inhibits	phenotype	0.70
APP	associated_with	gene	0.65
BACE1	associated_with	gene	0.65
ABCA1	associated_with	gene	0.65
CD33	associated_with	gene	0.65
CX3CR1	associated_with	gene	0.65
ABCA1	regulates	gene	0.65
APOE	regulates	gene	0.65
SPHINGOMYELIN	activates	phenotype	0.65
SPHINGOMYELIN	regulates	phenotype	0.65
TNF	inhibits	gene	0.65
TNF	regulates	gene	0.65
ALZHEIMER	associated_with	gene	0.65
AMYLOID	associated_with	gene	0.65
AUTOPHAGY	associated_with	gene	0.65
ASTROCYTE	associated_with	gene	0.65
ALS	associated_with	gene	0.65
ALZHEIMER	expressed_in	disease	0.65
ATP	regulates	gene	0.65
NEURON	targets	cell_type	0.65
CHOLESTEROL	encodes	phenotype	0.65
STROKE	targets	disease	0.65
ERK1	protects_against	gene	0.60
CDK5	protects_against	gene	0.60
EFAVIRENZ	modulates	drug	0.60
efavirenz	activates	drug	0.60
TAU	activates	gene	0.60
APP	regulates	gene	0.60
TAU	regulates	gene	0.60
APOE	activates	gene	0.60
BDNF	inhibits	gene	0.60
HUNTINGTIN	therapeutic_target	gene	0.60
LRP8	activates	gene	0.60
APOA1	activates	gene	0.60
MAPT	regulates	gene	0.60

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
CYP46A1 Overexpression Gene Therapy	0.631	neurodegeneration	Lipid raft composition changes in synapt
TREM2-Mediated Cholesterol Dysregulation in Microglial Senes	0.574	neurodegeneration	Gene expression changes in aging mouse b
CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microgli	0.569	neurodegeneration	Lipid raft composition changes in synapt
CYP46A1 Suppression for Tau-Mediated Neurodegeneration	0.494	neurodegeneration	Lipid raft composition changes in synapt

Mentioning Analyses (2)

Scientific analyses that reference this entity

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

neurodegeneration | 2026-04-02 | 5 hypotheses Top: 0.519

Lipid raft composition changes in synaptic neurodegeneration

neurodegeneration | 2026-04-01 | 12 hypotheses Top: 0.648

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
TREM2, microglia, and Alzheimer's disease. [PMID:33516818]	Qin Q, Teng Z, Liu C, Li Q, Yin Y, Tang	Mech Ageing Dev	2021	1
Complement and microglia mediate early synapse loss in Alzheimer mouse models. [PMID:27033548]	Hong S, Beja-Glasser VF, Nfonoyim BM, Fr	Science	2016	1
Potential Biological Processes Related to Brain SLC13A5 Across the Lifespan: Wei [PMID:41750164]	Ferreira BK, Schuck PF, Ferreira GC, Fre	Brain sciences	2026	0
How cytochrome P450 enzymes in humans are involved in Parkinson's disease: a lit [PMID:41730497]	Ren B, Yan H, Han C, Sun S, Wang D, Xu Y	Neuroscience	2026	0
Dysregulated Cholesterol Clearance via CYP46A1 Contributes to Cerebellar Sterol [PMID:41828569]	Tapia PJ, Rivera BI, Espinoza CS, Stolze	International journal of molec	2026	0
Efavirenz treatment improves retinal vaso-obliteration and pathological neovascu [PMID:41810243]	Bailey B, Rudd Zhong Manis J, Seth G, Ra	Frontiers in medicine	2026	0
Radiosynthesis and Evaluation of 18F‑Labeled Deuterated Radioligand for Positron [PMID:41704371]	Li Y, Song Z, Shi H, Zhao T, Chen J, Zho	ACS medicinal chemistry letter	2026	0
Streptozotocin and L-Buthionine-Sulfoximine Decrease Neuron Membrane Lipid Packi [PMID:40439741]	Martins YA, Cardinali CAEF, Costa AP, To	Neurotoxicity research	2025	0
Treatment with efavirenz extends survival in a Creutzfeldt-Jakob disease model b [PMID:40540390]	["Ali T", "Cashion J", "Hannaoui S", "Ah	JCI insight	2025	0
The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974]	Dai L, Wang J, Meng L, Zhang X, Xiao T,	PLoS biology	2025	0
Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the [PMID:40045480]	Griffiths L, Hawkins K, Yutuc E, Angelin	Brain pathology (Zurich, Switz	2025	0
Astrocyte-neuron combined targeting for CYP46A1 gene therapy in Huntington's dis [PMID:40859407]	Parsai LH, Chali F, Subashi E, Zeitouny	Acta neuropathologica communic	2025	0
Overexpression of cholesterol 24-hydroxylase CYP46A1 attenuates retinal dysfunct [PMID:40975483]	Long Z, Zhang J, Feng J, He T	Experimental eye research	2025	0
Cholesterol metabolic reprogramming mediates microglia-induced chronic neuroinfl [PMID:40987840]	Zhao Q, Li J, Feng J, Wang X, Liu Y, Wan	Nature metabolism	2025	0
Elevated 24-hydroxycholesterol levels counteract okadaic acid-induced tau hyperp [PMID:40653030]	Giannelli S, Eroli F, Loera-Valencia R,	Neurobiology of disease	2025	0
Mesenchymal stem cells overexpressing CYP46A1 inhibit lipopolysaccharide-induced [PMID:40609611]	Shao Y, Ma B, Jin R, Kong N, Tang J, Li	European journal of pharmacolo	2025	0
ABC Transporters, APOE, CYP46A1, and LRP1 Gene Polymorphisms as Markers of Demen [PMID:41226793]	Machowska M, Leszek J, Rączy-Krzemianows	International journal of molec	2025	0
Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hall [PMID:38142760]	Nunes MJ, Carvalho AN, Reis J, Costa D,	Biochimica et biophysica acta.	2024	0
CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition [PMID:38266095]	Latorre-Leal M, Rodriguez-Rodriguez P, F	Science advances	2024	0

CYP46A1

Understanding Entity Pages

Summary

Wiki Pages (21)

CYP46A1 — Cholesterol 24-Hydroxylase

AAV Gene Therapy for Neurodevelopmental Epilepsy — Competitive Landscape & Delivery Alternatives

Parkinson's Disease

Therapeutics

NPM1 Gene

Section 162: Advanced Antioxidant and Redox Therapy in CBS/PSP

coq10-neurodegeneration

Growth Factor Therapies

omega-3-fatty-acids-neurodegeneration

Coenzyme Q10 for Neurodegeneration

deferiprone-neurodegeneration

vitamin-d-therapy-neurodegeneration

TDP-43 Proteinopathy

Neuroprotection Strategies in Neurodegeneration

Curcumin for Neurodegeneration

Mediterranean and MIND Diets for Neurodegeneration

creatine-supplementation-neurodegeneration

Section 153: Virtual Reality Therapy Protocols in CBS/PSP

Ambroxol for Neurodegeneration (GCase Chaperone Strategy)

Metabolomic Alterations in PSP

NAD+ Precursors for Neurodegeneration