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Literature summary for 1.14.14.25 extracted from

  • Hudry, E.; Van Dam, D.; Kulik, W.; De Deyn, P.P.; Stet, F.S.; Ahouansou, O.; Benraiss, A.; Delacourte, A.; Bougneres, P.; Aubourg, P.; Cartier, N.
    Adeno-associated Virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimers disease (2010), Mol. Ther., 18, 44-53.
    View publication on PubMedView publication on EuropePMC
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Cloned(Commentary)

Cloned (Comment) Organism
adeno-associated vectors expressing wild-type (AAV5-wtCYP46A1) or mutated (AAV5-mtCYP46A1) CYP46A1 cDNA tagged with the hemaglutinin epitope injected in hippocampus, frontal, and parietal cortices of both hemispheres of 3-month-old APP23 mice. AAV5-wtCYP46A1 vector injection in the cortex and hippocampus of amyloid precursor protein/presenilin 1 mice. Overexpression in N2a-APP17 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
A1309C destroys its heme structure, resulting in the complete lack of cholesterol 24-hydroxylase activity Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
 APP23 mouse
-
Mus musculus APP23
-
 APP23 mouse
-

Source Tissue

Source Tissue Comment Organism Textmining
additional information N2a cell line Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
-
 Mus musculus (24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
-
 Homo sapiens (24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
cholesterol + [reduced NADPH-hemoprotein reductase] + H+ + O2
-
 Mus musculus APP23 (24S)-24-hydroxycholesterol + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Synonyms

Synonyms Comment Organism
CYP46A1
-
 Mus musculus
CYP46A1
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
 Mus musculus
NADPH
-
 Homo sapiens

General Information

General Information Comment Organism
physiological function overexpression of human CYP46A1 gene does not modify the expression of endogenous murine Cyp46A1 gene Mus musculus
physiological function selective overexpression of CYP46A1 in neurons can reduce Abeta peptides and amyloid deposits in mouse models of Alzheimer's disease when the overexpression of CYP46A1 is induced before or after the formation of amyloid plaques. Injection of adeno-associated vector encoding CYP46A1 in the cortex and hippocampus of APP23 mice before the onset of amyloid deposits markedly reduces Abeta peptides, amyloid deposits and trimeric oligomers at 12 months of age. Neuronal overexpression of CYP46A1 decreases microgliosis and astrocytosis and improves cognitive deficits in APP23 mice. AAV5-wtCYP46A1 vector injection in the cortex and hippocampus of amyloid precursor protein/presenilin 1 mice after the onset of amyloid deposits also reduces markedly the number of amyloid plaques in the hippocampus, and to a less extent in the cortex, 3 months after the injection Homo sapiens