シトクロムP450と神経変性疾患

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3型(化学毒素)毒性学・薬理学デトックス

CYPフォーム

は  

脳のシトクロムP450

シトクロムP450は酵素は、細菌、植物、哺乳動物などほとんどすべての生物に存在する酸化酵素。

一般的に薬物、有機化合物など生体の異物を代謝させて排出する解毒プロセスの第一段階を担当する解毒酵素として認識されている。

しかし、これらの酵素は多くの内因性の基質を代謝し、生理学的に重要な役割も果たしている。

脳内でもさまざまなCYPアイソフォームが発現しており、コレステロールの代謝サイクル、ドーパミン、セロトニン、モルヒネ、ホルモン、保護作用をもつ脂質中間体の生合成に関与する。これまでの研究から、これらの酵素群が脳の恒常性維持に不可欠であるという証拠が積み重なっている。

 

潜在的には、すべてのCYP酵素が神経変性疾患と関連する可能性があるが、研究で神経変性疾患と関連づけられているCYP酵素は、以下の通り。

  • CYP46A1 脳内コレステロールの排出
  • CYP17A1 プレグネノロン-DHEA代謝
  • CYP19A1 アロマターゼ酵素の形成
  • CYP2C19(阻害)アラキドン酸の代謝物抑制による保護効果
  • CYP2D6 ドーパミン代謝(パーキンソン病)
  • CYP2E1 MPTP毒素の解毒(パーキンソン病)

 

ラットの脳ではシトクロムP450の含有量は肝臓の3%であり、30倍低い活性を有する。

脳内のCYP発現は不均一であり、一部のCYP(CYP46A1、CYP2D6)は肝臓よりも脳内でより大きな割合で発現する。

CYP1A1、2B、2E1、3Aなどの一部のアイソフォームは主にニューロンで見られるが、CYP2D6などの他のアイソフォームはニューロンとグリア細胞の両方で見られる。

CYP1Aファミリー

CYP1Aファミリーは、発がん性物質、ホルモン、医薬品の代謝に関与する。

多環芳香族炭化水素(PAH)の発癌性生物活性、複素環式芳香族アミン/アミド、ポリ塩化ビフェニル(PCB)、他の環境毒素と関連することが知られている。

CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies - PubMed
CYP1A1 and 1A2 play critical roles in the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines/amides (...
Effects of Food Natural Products on the Biotransformation of PCBs - PubMed
Many food products, particularly fruits and vegetables, contain natural products that affect biotransformation enzymes. These may be expected to affect the rate...

CYP1A酵素群は、フェーズⅡと協調されずに過剰活性されると発がん性をもつ環境因子の毒性効果を高める可能性がある。

Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk - PubMed
The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances includi...

CYP1酵素(+CYP1B1)は、エストロゲン代謝産物の形成にも関与する。

Cytochrome P450-mediated metabolism of estrogens and its regulation in human - PubMed
Estrogens are eliminated from the body by metabolic conversion to estrogenically inactive metabolites that are excreted in the urine and/or feces. The first ste...

CYP1A1

誘導剤

レスベラトロール

前臨床試験 レスベラトロールによるCYP1A1の促進

Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study - PubMed
Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologi...

クルクミン

Curcumin implants, not curcumin diet, inhibit estrogen-induced mammary carcinogenesis in ACI rats - PubMed
Curcumin is widely known for its antioxidant, anti-inflammatory, and antiproliferative activities in cell-culture studies. However, poor oral bioavailability li...
Curcumin content of turmeric and curry powders - PubMed
Curcumin, derived from the rhizome curcuma longa, is one of the primary ingredients in turmeric and curry powders that are used as spices in Middle Eastern and ...

大豆

The influence of soybean extract on the expression level of selected drug transporters, transcription factors and cytochrome P450 genes encoding phase I drug-metabolizing enzymes - PubMed
Our results suggest that Glycine max may change the expression level of CYPs, especially CYP3A4 and CYP1A 7, involved in biotransformation of xenobiotics (drugs...

ニンニク

The combined effects of garlic oil and fish oil on the hepatic antioxidant and drug-metabolizing enzymes of rats - PubMed
This present study was designed to investigate the combined modulatory effect of garlic oil (GO) and fish oil (FO) on the antioxidant and drug metabolism system...

フィッシュオイル(高用量)

Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns - PubMed
The ability of rosemary to modulate cytochrome P450 (CYP) and detoxication enzymes in rat liver was evaluated by comparing the effects of dried leaves and leaf ...

ローズマリー

Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns - PubMed
The ability of rosemary to modulate cytochrome P450 (CYP) and detoxication enzymes in rat liver was evaluated by comparing the effects of dried leaves and leaf ...

アスタキサンチン、酵母、オキアミ

Effects of canthaxanthin, astaxanthin, lycopene and lutein on liver xenobiotic-metabolizing enzymes in the rat - PubMed
1. The catalytic activities of several phase I and II xenobiotic-metabolizing enzymes and the immunochemical detection of P4501A and 2B have been investigated i...

阻害剤

エラグ酸・ベリー類

Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application
Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the eff...

グレープフルーツジュース

Inhibition of human and rat CYP1A1 enzyme by grapefruit juice compounds - PubMed
Cytochrome P4501A1 is involved in the metabolism of carcinogenic polycyclic aromatic hydrocarbons; therefore, its inhibition interferes with the carcinogenesis ...

トマト、人参に含まれる赤い色素

The carotenoid lycopene differentially regulates phase I and II enzymes in dimethylbenz[a]anthracene-induced MCF-7 cells - PubMed
The present study illustrated that phase I enzyme inhibition and phase II enzyme induction were the underlying chemoprotective mechanisms of lycopene against PA...

スルフォラファン(ブロッコリー)

Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro - PubMed
Increasing environmental pollution by carcinogens such as some of persistent organic pollutants (POPs) has prompted growing interest in searching for chemopreve...

緑茶抽出物

Comparative studies on the effects of green tea extracts and individual tea catechins on human CYP1A gene expression - PubMed
Green tea possesses significant anticancer activity in numerous experimental animal models, including demonstrated protection against aryl hydrocarbon induced c...

ローズマリー

Carnosol, a Constituent of Zyflamend, Inhibits Aryl Hydrocarbon Receptor-Mediated Activation of CYP1A1 and CYP1B1 Transcription and Mutagenesis
The aryl hydrocarbon receptor (AhR), a ligand-activated member of the basic-helix-loop-helix family of transcription factors, plays a significant role in polycy...

CYP1A2

カフェインを代謝する酵素として有名。CYP1A2の発現はタバコの煙に含まれる多環芳香族炭化水素(PAH)によって誘導される。

他の生体異物基質にはアフラトキシンB1、パラセタモール(アセトアミノフェン)が含まれる。

CYP1A2 - Wikipedia

CYP1A2の活性は、精巣腫瘍リスクの増加と関連する。

Low CYP1A2 activity associated with testicular cancer - PubMed
The incidence rate of testicular cancer has increased during the last 50 years. An interplay between changing environmental factors and individual susceptibilit...

誘導剤

アブラナ科野菜

(インドール3カルビノールのCYP1A2活性)

Induction of estradiol metabolism by dietary indole-3-carbinol in humans - PubMed
Dietary indoles in cruciferous vegetables induce cytochrome P450 enzymes and have prevented tumors in various animal models. Because estradiol metabolism is als...
CYP1A2, GSTM1, and GSTT1 polymorphisms and diet effects on CYP1A2 activity in a crossover feeding trial - PubMed
Cytochrome P-450 1A2 (CYP1A2) is a biotransformation enzyme that activates several procarcinogens. CYP1A2 is induced by cruciferous and inhibited by apiaceous v...
Modulations of P450 mRNA in liver and mammary gland and P450 activities and metabolism of estrogen in liver by treatment of rats with indole-3-carbinol - PubMed
Indole-3-carbinol (I3C), found in cruciferous vegetables, has been shown to suppress tumorigenesis at estrogen-responsive sites. This effect may be mediated thr...

緑茶

Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats - PubMed
The effect of commercially available green tea (GT) and black tea (BT) drinks on drug metabolizing enzymes (DME) and oxidative stress in rats was investigated. ...
Selective induction of rat hepatic CYP1 and CYP4 proteins and of peroxisomal proliferation by green tea - PubMed
Rats were exposed to freshly prepared aqueous extracts of green tea (2.5% w/v) as the sole source of drinking water for 4 weeks. Hepatic cytochrome P450 activit...

活性の阻害

ケルセチン

ケール

ニンニク

にんにくオイルはマウスのCYP1A2を抑制する。

The modulatory effects of garlic oil on hepatic cytochrome P450s in mice - PubMed
In order to probe into the effects of garlic oil (GO) on the hepatic CYP2E1, CYP1A2 and CYP3A, male Kun-Ming mice were treated with GO (100 mg/kg body weight) o...

大豆(ダイゼイン)

Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers - PubMed
Daidzein, a principal isoflavone in soybean, in higher doses may inhibit CYP1A2 activity in vivo, and physicians should be aware of potential drug-food interact...

グレープフルーツ、ナリンゲニン

300mlのグレープフルーツジュースとナリンゲニンはヒトのCYP1A2活性を阻害する

Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers - PubMed
Daidzein, a principal isoflavone in soybean, in higher doses may inhibit CYP1A2 activity in vivo, and physicians should be aware of potential drug-food interact...

CYP1B1

多環式芳香族炭化水素や17βエストラジオールなどの発癌物質を代謝する。

CYP1B1 - Wikipedia

ルイボス茶、セロリ(クリソエリオール)によるCYP1B1の選択的阻害

Breast cancer and flavonoids - a role in prevention - PubMed
Endogenous estrogens, such as 17β-estradiol (E2), are implicated in the development of breast cancer. The putative mechanisms by which estrogens exert the carci...

Cyp1B1発現はNF-κB活性を抑制することにより血管新生を促進する。

Cyp1B1 expression promotes angiogenesis by suppressing NF-κB activity
Nuclear factor-κB (NF-κB) is a master regulator of genes that control a large number of cellular processes, including angiogenesis and inflammation. We recently...

CYP2Aファミリー

CYP2ファミリーは、薬物、生体異物、ホルモン、ケトン類、グリセロール、脂肪酸などの他の内因性化合物の代謝に関与する。

The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans - PubMed
Cytochrome p450s comprise a superfamily of heme-thiolate proteins named for the spectral absorbance peak of their carbon-monoxide-bound species at 450 nm. Havin...

CYP2A6

ニコチン、クマリンの代謝に関わるCYP酵素

ケルセチン 、りんご、アプリコット、ブルーベリー、黄タマネギ、ケール、アルファルファもやし、インゲン、ブロッコリー、紅茶、チリパウダー 、ブロッコリー

誘導剤

クルクミン

Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers - PubMed
The results indicated that curcumin inhibits CYP1A2 function but enhances CYP2A6 activity. Simultaneously, some pharmacokinetic parameters relating to 17X were ...

阻害剤

アーモンド抽出物

More potent inhibition of human CYP2A6 than mouse CYP2A5 enzyme activities by derivatives of phenylethylamine and benzaldehyde - PubMed
1. A rapid 96-well plate assay method was developed and validated to measure liver microsomal coumarin 7-hydroxylation in vitro. 2. The method was used to test ...

シナモン精油(シンナムアルデヒド)

Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole
Human exposure to trans-cinnamic aldehyde is common through diet and through the use of cinnamon powder for diabetes and to provide flavor and scent in commerc...

ホワイトグレープフルーツ

Effect of grapefruit juice on cytochrome P450 2A6 and nicotine renal clearance - PubMed
Grapefruit juice inhibits the metabolism of nicotine to cotinine, a pathway mediated by CYP2A6, and increases the renal clearance of nicotine and cotinine. Nico...
CYP2A6 - HerbPedia

CYP2B6

薬剤の排出

Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance - PubMed
Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both between individuals and within indi...

誘導剤

阻害剤

甘草(グラブリジン)(強力)

http://herbpedia.wdfiles.com/local–files/attachments/herbal_bioactivation_mini_review.pdf

ボルネオール(マンゴージンジャーオイル)

CYP2B6 - HerbPedia

CYP2C8

CYP2C8は、肝臓CYPの7%を占める。

CYP2C8ハプロタイプ構造にはかなりの人種的多様性がある

ロシグリタゾン、ピオグリタゾンはCYP2C8 により肝臓で代謝される。

Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone - PubMed
CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglit...

CYP2C8は、スタチン製剤セリバスタチンの代謝に大きく関与し、フルバスタチンとシンバスタチン酸の代謝に控えめな役割を果たすと考えられている。

CYP2C8多型は、NSAIDの代謝に影響を与える可能性がある。

Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies
Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many clinically available drugs from a diverse number of drug classes (e.g., thiazolidi...

CYP2C9

薬の最大15から20パーセントの代謝クリアランスの原因であると推定されている。

CYP2C9によって代謝される薬剤

  • イルベサルタン、
  • ロサルタン アンジオテンシンIIブロッカー
  • フェニトイン 抗てんかん薬
  • シクロホスファミド アルキル化剤
  • タモキシフェン 抗エストロゲン
  • フルバスタチン スタチン
  • セレコキシブ NSAID
  • ジクロフェナク NSAID
  • イブプロフェン NSAID
  • ロルノキシカム NSAID
  • メロキシカム NSAID
  • ナプロキセン NSAID
  • グリベンクラミド スルホニル尿素
  • グリメピリド スルホニル尿素
  • グリピジド スルホニル尿素
  • トルブタミド スルホニル尿素
  • ワルファリン 抗凝固剤
CYP2C9 polymorphisms: considerations in NSAID therapy - PubMed
The increased focus on safety in clinical trials represents a formidable hurdle regarding the availability of marketed drugs. The lengthy experimental process o...
Cytochrome P450 2C9-CYP2C9

CYP2C9はリファンピシンによって誘発される。

 

ワルファリン

誘導剤

葉酸

Effects of folic acid supplementation on the pharmacokinetics and anticoagulant effect of warfarin: an open-label, prospective study of long-term administration in adults - PubMed
Folic acid supplementation was associated with significantly increased formation clearance of (S)-7-hydroxywarfarin. Changes in warfarin dosage requirements and...

セントジョーンズワート

Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures - PubMed
St. John's wort extract (SJW) (Hypericum perforatum L.) is among the most commonly used herbal medications in the United States. The predominance of clinical re...

PXRの活性化による潜在的なCYP2C9誘導剤

  • ハマヨモギ
  • アルテミシニン
  • ビャクジュツ(オオバナオケラ)
  • ベルベリン塩酸
  • カフェストール
  • 中国アンジェリカ
  • オウレンキネンシス
  • クルクミン
  • イカリソウ
  • オイゲノール
  • クチナシの果実
  • イチョウ
  • ググルステロン
  • 川芎(Ligusticum chuanxiong)
  • リグスチリド
  • ルテオリン
  • キョウチクトウ
  • ミルクシスル(オオアザミ)
  • ジャノヒゲ
  • シャクヤクlactiflora
  • ツルドクダミ
  • アカヤジオウの根(地黄)
  • レスベラトロール
  • 朝鮮五味子
  • シザンテリン A
  • キカラスウリ
  • ターメリック
CYP2C9 - HerbPedia

阻害剤

レスベラトロール(強力)

Resveratrol Modulates Drug and Carcinogen Metabolizing Enzymes in a Healthy Volunteer Study
Resveratrol has been shown to exhibit cancer preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologi...

ベルベリン

Repeated administration of berberine inhibits cytochromes P450 in humans
Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have repo...

甘草

http://herbpedia.wdfiles.com/local–files/attachments/herbal_bioactivation_mini_review.pdf

CYP2C19

プロトンポンプ阻害薬、抗てんかん薬など、生体異物の代謝に関与する。

臨床で使用される薬物の10%に作用する肝臓酵素。

エポキシゲナーゼ活性があり、脂質代謝に関わる。

アルツハイマー病への変異体保護効果

CYP2C19遺伝子多型のアルツハイマー病患者では、アミロイドβの負荷が減少しており、変異体が保護効果を示す。

推定されるメカニズムは、CYP2C19がエストラジオールの触媒作用に関与しており、遺伝子多型によりエストロゲンの異化作用が低下することでエストロゲンの有益な効果がアミロイドβ産生におよぶとするもの。

もうひとつは、アラキドン酸の代謝物であるエポキシエイコサトリエン酸(EET)は、血流、皮質血管新生の調整、抗炎症反応などに有益な効果があることが示されており、CYP2C19変異がアラキドン酸の他の経路によって代謝されることで、EETの産生が減少し保護効果が失われるというもの。

rs4388808

CYP2C19 variant mitigates Alzheimer disease pathophysiology in vivo and postmortem
To verify whether CYP polymorphisms are associated with amyloid-β (Aβ) pathology across the spectrum of clinical Alzheimer disease using in vivo and postmortem ...

阻害剤

レスベラトロール

Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects - PubMed
The above data suggest that GBE, when taken in normally recommended doses over a 4-week time period, may not affect the pharmacokinetics of diazepam via CYP2C19...

セントジョーンズワート

Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes - PubMed
The aim of this study was to evaluate in vitro the dose-dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic...

誘導剤

アスピリン

Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects - PubMed
The effect of low-dose aspirin on CYPs was enzyme-specific. Both 7-day and 14-day low-dose aspirin induced the in vivo activities of CYP2C19 but did not affect ...

イチョウ

Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes - PubMed
The aim of this study was to evaluate in vitro the dose-dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic...

セージ

Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes - PubMed
The aim of this study was to evaluate in vitro the dose-dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic...

セントジョーンズワート

Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes - PubMed
The aim of this study was to evaluate in vitro the dose-dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic...

バレリアンルート

Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes - PubMed
The aim of this study was to evaluate in vitro the dose-dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic...

CYP2D6

CYP2D6は、脳の様々な領域の神経細胞、グリア細胞で発現しており、神経保護酵素として考えられている。

ドーパミン合成

CYP2Dを介した脳内でのチラミンからのドーパミン合成がin vitro、in vivoで示されておりCYP2D6多型は、パーキンソン病と肺がんに関連している可能性がある。

ドーパミンやセロトニンバランスに関与することで、ヒトの性格や行動特性に影響を与える。

Relation between CYP2D6 genotype, personality, neurocognition and overall psychopathology in healthy volunteers - PubMed
In the studied population of healthy volunteers, PMs versus EMs showed lower vulnerability to psychopathology and greater impulsivity. Moreover, differences in ...
CYP2D6 genotyping for psychiatric patients treated with risperidone: considerations for cost-effectiveness studies - PubMed
In order to ascertain data availability and feasibility for conducting cost-effectiveness studies in pharmacogenetics, and as part of a European Commission Join...
セロトニン合成

5-MTから5-HTへのO-脱メチル化は、肝臓/脳ミクロソームにおけるヒトおよびラットcDNA発現CYP2Dアイソフォームについてin vitroで報告されている。

The catalytic competence of cytochrome P450 in the synthesis of serotonin from 5-methoxytryptamine in the brain: an in vitro study - PubMed
Brain serotonin has been implicated in the pathophysiology of a wide spectrum of psychiatric disorders, as well as in the mechanism of action of psychotropic dr...
パーキンソン病の保護CYP

CYP2D6は年齢とともに脳内で増加するが、パーキンソン病患者では低下する。

CYP2D6は農薬の代謝に関与しており、CYP2D6の遺伝的多型による酵素活性の低下がパーキンソン病発症リスクを高めることはよく知られている。

Cytochrome P450 2D6 and Parkinson's Disease: Polymorphism, Metabolic Role, Risk and Protection - PubMed
Cytochrome P450 (CYP) 2D6 is one of the most highly active, oxidative and polymorphic enzymes known to metabolize Parkinsonian toxins and clinically established...

CYP2D6

レスベラトロール(高用量)

Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study - PubMed
Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologi...

ガーデンクレス(コショウソウ)

胡椒のような辛味があるアブラナ科野菜

Effect of Garden Cress Seeds Powder and Its Alcoholic Extract on the Metabolic Activity of CYP2D6 and CYP3A4 - PubMed
The powder and alcoholic extract of dried seeds of garden cress were investigated for their effect on metabolic activity of CYP2D6 and CYP3A4 enzymes. In vitro ...

ケール

CYP2D6への抑制効果

Inhibitory effects of kale ingestion on metabolism by cytochrome P450 enzymes in rats - PubMed
Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-pro...

CYP2E1

発がん物質の活性化

CYP2E1は、ハロタン、イソフルラン、クロルゾキサゾン、エタノールなどの神経系薬を代謝し、発がん性ニトロソアミンおよびアフラトキシンB1を生物活性させる。また基質に関係なくフリーラジカルを生成する。

The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans - PubMed
Cytochrome p450s comprise a superfamily of heme-thiolate proteins named for the spectral absorbance peak of their carbon-monoxide-bound species at 450 nm. Havin...

CYP2E1多型は冠動脈疾患、胃癌リスクと関連する。

Cytochrome P4502E1 (CYP2E1) genetic polymorphisms in a Lebanese population: frequency distribution and association with morbid diseases - PubMed
This is the first study on the genetic polymorphism of CYP2E1 in a Lebanese population. These data will be useful for future assessment of the role of CYP2E1 po...
Genetic susceptibility and gastric cancer risk - PubMed
The aim of the present paper is to review and evaluate, in a comprehensive manner, the most recent published evidence on the contribution of genetic susceptibil...

CYP2E1によって誘発される酸化ストレスは、GLUT4発現の抑制を介してインスリン作用の障害を引き起こすことも示されている。

CYP2E1 impairs GLUT4 gene expression and function: NRF2 as a possible mediator - PubMed
Impaired GLUT4 function/expression in insulin target tissues is well-documented in diabetes and obesity. Cytochrome P450 isoform 2E1 (CYP2E1) induces oxidative ...
パーキンソン病

CYP2E1は、MPTP毒性の増強と関連しており、パーキンソン病リスクを高める可能性がある。

Cytochrome P450 and Parkinson's disease: protective role of neuronal CYP 2E1 from MPTP toxicity - PubMed
Elucidation of the biochemical steps leading to the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-induced degeneration of the nigro-striatal dopamine (DA)...

パーキンソン病患者の脳ではCYP2E1のDNAメチル化が低下を示す。

Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1 - PubMed
Multiple lines of evidence suggest a link between environmental toxins and Parkinson's disease (PD). Although numerous studies reported associations of genetic ...

誘導剤

中鎖トリグリセリド(MCTオイル)

Role of medium-chain triglycerides in the alcohol-mediated cytochrome P450 2E1 induction of mitochondria - PubMed
Mitochondria participate in the induction of CYP2E1 by alcohol and contribute to lipid peroxidation and GSH depletion. Thus, lipid composition of the diet is an...

ニコチン

The Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System
Ethanol consumption has effects on the central nervous system (CNS), manifesting as motor incoordination, sleep induction (hypnosis), anxiety, amnesia, and the ...

絶食

CYP2E1 autoantibodies in liver diseases
Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but ar...

オメガ3多価不飽和脂肪酸

CYP2E1 - Wikipedia

アルコール

The Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System
Ethanol consumption has effects on the central nervous system (CNS), manifesting as motor incoordination, sleep induction (hypnosis), anxiety, amnesia, and the ...

NAFLD

Role of CYP2E1 in mitochondrial dysfunction and hepatic tissue injury in alcoholic and non-alcoholic diseases
Alcoholic fatty liver diseases (AFLD) and non-alcoholic fatty liver diseases (NAFLD) are two pathological conditions that are spreading worldwide. Both conditio...

阻害剤

レスベラトロール

Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers - PubMed
The purpose of the present study was to investigate the effect of resveratrol (RSV) pretreatment on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone...

ケルセチン

Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO - PubMed
Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metaboli...
Pioglitazone, quercetin and hydroxy citric acid effect on cytochrome P450 2E1 (CYP2E1) enzyme levels in experimentally induced non alcoholic steatohepatitis (NASH) - PubMed
Being a powerful antioxidant, quercetin offers absolute protection to liver against NASH by reducing the levels of CYP2E1 and, thereby, reducing CYP2E1 mediated...

クレソン

Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress - PubMed
To investigate the effect of watercress on the metabolism of chlorzoxazone, an in vivo probe for CYP2E1, the oral pharmacokinetics of chlorzoxazone was studied ...

にんにく

Garlic oil alleviated ethanol-induced fat accumulation via modulation of SREBP-1, PPAR-α, and CYP2E1 - PubMed
Garlic oil (GO) has been shown to partially attenuate ethanol-induced fatty liver, but the underlying mechanisms remain unclear. The current study was designed ...
Anticarcinogenic effect and modification of cytochrome P450 2E1 by dietary garlic powder in diethylnitrosamine-initiated rat hepatocarcinogenesis - PubMed
The purpose of this study was to determine the effects of dietary garlic powder on diethylnitrosamine (DEN)- induced hepatocarcinogenesis and cytochrome P450 (C...
Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application
Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the eff...

N-アセチルシステイン

 

エラグ酸

A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat
The present study was designed to evaluate different doses of ellagic acid (EA) in vivo in rats for its potential to modulate hepatic phases I, II, and antioxid...

緑茶・紅茶

Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats - PubMed
The effect of commercially available green tea (GT) and black tea (BT) drinks on drug metabolizing enzymes (DME) and oxidative stress in rats was investigated. ...

クリシン

 

クルクミン

Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK - PubMed
These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating th...

ピペリン

Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers - PubMed
1. The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in hea...

たんぽぽ抽出物

Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in Sprague-Dawley rats - PubMed
The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. ...

丹参

Danshen (Salvia miltiorrhiza) water extract inhibits paracetamol-induced toxicity in primary rat hepatocytes via reducing CYP2E1 activity and oxidative stress - PubMed
DSE protected hepatocytes against APAP-induced injury via maintenance of mitochondrial metabolic activity, CYP2E1 inhibition, reduction of total glutathione dep...

CYP3

CYP3Aアイソフォームの発現は組織特異的。

誘導剤

ルイボス茶、ニンニク、魚油

阻害剤

緑茶、紅茶、ケルセチン

CYP3A4

病院で処方される薬剤の50%以上を除去する重要なCYP酵素。

Identifying cytochrome p450 functional networks and their allosteric regulatory elements - PubMed
Cytochrome P450 (CYP) enzymes play key roles in drug metabolism and adverse drug-drug interactions. Despite tremendous efforts in the past decades, essential qu...

カフェイン、テストステロン、プロゲステロン、アンドロステンジオンはCYP3A4酵素系の基質であり、多くの食品やサプリメントはこの酵素活性を低下させる。

このCYP3A4酵素活性は幅広く個人差があるため、高用量であったり複数の薬物投与、食品摂取、ハーブの相互作用はリスクをもたらしうる。

誘導剤

セントジョーンズワート

The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials
The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John’s wort extracts on the metabolis...
Saint John's wort, an herbal inducer of the cytochrome P4503A4 isoform, may alleviate symptoms of Willis-Ekbom's disease - PubMed
Results of this trial suggest that Saint John's wort may benefit some Willis-Ekbom's disease patients. However, as this trial was not placebo-controlled, the ex...

カプサイシン

Effects of capsicine on rat cytochrome P450 isoforms CYP1A2, CYP2C19, and CYP3A4 - PubMed
Due to the frequent consumption of capsaicin (CAP) and its current therapeutic application, the correct assessment of this compound is important from a public h...
Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer-binding protein β activation - PubMed
From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBPβ. Ou...

ビタミンD

Interplay between Vitamin D and the Drug Metabolizing Enzyme CYP3A4
Cytochrome P450 3A4 (CYP3A4) is a multifunctional enzyme involved in both xenobiotic and endobiotic metabolism. This review focuses on two aspects: regulation o...

クルクミン

タバコ 多環芳香族炭化水素(PAH)

Polycyclic aromatic hydrocarbons stimulate human CYP3A4 promoter activity via PXR - PubMed
Metabolic activation of polycyclic aromatic hydrocarbons (PAH) is mediated mainly by cytochrome P₄₅₀ monooxygenases (CYP) CYP1A1, 1A2 and 1B1. Several PAH are k...

アフラトキシンB1

Aflatoxins upregulate CYP3A4 mRNA expression in a process that involves the PXR transcription factor - PubMed
Pregnane X receptor (PXR) is a member of the nuclear hormone receptor (NHR) superfamily, which regulates xenobiotic and endobiotic metabolism in the liver. This...

阻害剤

グレープフルーツジュース

Interactions between grapefruit juice and cardiovascular drugs - PubMed
Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by ...
Interactions between grapefruit juice and cardiovascular drugs - PubMed
Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by ...

レスベラトロール

ケール

Inhibitory effects of kale ingestion on metabolism by cytochrome P450 enzymes in rats - PubMed
Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-pro...

ベルベリン

Repeated administration of berberine inhibits cytochromes P450 in humans - PubMed
Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berbe...

ケルセチン

Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and Centella asiatica in Human Liver Microsomes - PubMed
Withania somnifera is commonly used as a rejuvenator, whereas Centella asiatica is well known for its anxiolytic and nootropic effects. The present study aims a...

ピペリン

Co-Administration of Piperine and Docetaxel Results in Improved Anti-Tumor Efficacy via Inhibition of CYP3A4 Activity
Docetaxel is the mainline treatment approved by the FDA for castration-resistant prostate cancer (CRPC) yet its administration only increases median survival by...
Altered CYP expression and function in response to dietary factors: potential roles in disease pathogenesis - PubMed
Increasing evidence implicates dietary factors in the progression of diseases, including certain cancers, diabetes and obesity. Diet also regulates the expressi...

アピゲニン

Interactions between CYP3A4 and Dietary Polyphenols
The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobioti...

ミルクシスル

Milk thistle's active components silybin and isosilybin: novel inhibitors of PXR-mediated CYP3A4 induction - PubMed
Because cancer is often treated with combination therapy, unexpected pharmacological effects can occur because of drug-drug interactions. Several drugs are able...

EGCG

In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients - PubMed
The herbal remedies Natto K2, Agaricus, mistletoe, noni juice, green tea and garlic, frequently used by cancer patients, were investigated for their in vitro in...

コショウソウ

Effect of Garden Cress Seeds Powder and Its Alcoholic Extract on the Metabolic Activity of CYP2D6 and CYP3A4
The powder and alcoholic extract of dried seeds of garden cress were investigated for their effect on metabolic activity of CYP2D6 and CYP3A4 enzymes. In vitro ...

ブロッコリー(スルフォラファン)

The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor - PubMed
Sulforaphane (SFN) is a biologically active phytochemical found abundantly in broccoli. SFN has been promoted as a putative chemopreventive agent to reduce canc...

ブラックコホシュ

オリーブオイル(オレウロペイン)

Altered CYP expression and function in response to dietary factors: potential roles in disease pathogenesis - PubMed
Increasing evidence implicates dietary factors in the progression of diseases, including certain cancers, diabetes and obesity. Diet also regulates the expressi...

クランベリー

エキナセア

高麗人参(ジンセノサイドRd)

The inhibitory effects of herbal components on CYP2C9 and CYP3A4 catalytic activities in human liver microsomes - PubMed
Herbal medicines are widely consumed by patients in different clinical settings in the United States and all over the world. In this study, 7 herbal components ...

CYP3A5

その他のCYP450と同様、ほとんどが前立腺と肝臓で発現している。肝臓シトクロムの30%を担っている。遺伝的変異があり民族によって異なる。

CYP3A5 - Wikipedia
Role of Protein–Protein Interactions in Cytochrome P450-Mediated Drug Metabolism and Toxicity
Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein–p...

誘導剤

セイヨウオトギリソウ

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements
The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of a...

阻害剤

 

CYP4

CYP4ファミリーは、薬物代謝において役割を果たすと考えられているが、あまり詳細には解明されていない。

クロフィブラート、シプロ(脂質低下薬)、NSAIDは、プロスタグランジン、フタル酸エステルなどの毒物と関連する肝臓外のシトクロムファミリーであると理解されている。

The cytochrome P450 4 (CYP4) family - PubMed
1. The CYP4 family consists of 11 subfamilies (CYP4A-CYP4M), which encode constitutive and inducible isozymes expressed in both mammals and insects. 2. The CYP4...

CYP4A1

CYP4A1の遺伝的欠損は、20HETE形成の障害、血液脳関門の破壊、血管認知障害の発症に寄与する可能性がある。

Impaired myogenic response and autoregulation of cerebral blood flow is rescued in CYP4A1 transgenic Dahl salt-sensitive rat - PubMed
We have reported that a reduction in renal production of 20-HETE contributes to development of hypertension in Dahl salt-sensitive (SS) rats. The present study ...

誘導剤

緑茶抽出物

CYP4B1

CYP4B1アイソフォームは、MCTオイル(中鎖トリグリセリド)の代謝、および肺毒性および発がん性化合物の生物活性化に関与する。

CYP4B1: an enigmatic P450 at the interface between xenobiotic and endobiotic metabolism - PubMed
CYP4B1 belongs to the mammalian CYP4 enzyme family that also includes CYP4A, 4F, 4V, 4X, and 4Z subfamilies. CYP4B1 shares with other CYP4 proteins a capacity t...

このサブグループの多型および過剰発現は、膀胱がん、大腸炎と関連している可能性がある。大腸炎とCYP4B1活性の関連性を調べ、カフェイン含有食品に見られるカフェイン酸によるCYP4B1活性の促進が大腸炎疾活動の低下、抗炎症作用と相関することを発見された。

Increased CYP4B1 mRNA is associated with the inhibition of dextran sulfate sodium-induced colitis by caffeic acid in mice - PubMed
Susceptibility to inflammatory bowel diseases depends upon interactions between the genetics of the individual and induction of chronic mucosal inflammation. We...

CYP7~27

内因性の物質の代謝はCYP7~27ファミリーが含まれ、ステロイドや、脂溶性ビタミンに対して高い基質特性を示す。

CYP7A1

コレステロール代謝に重要なCYP7A1遺伝子によってコードされる酵素。コレステロール7α-ヒドロキシラーゼとも呼ばれ、胆汁酸合成、コレステロールレベルの調節に関わる。(胆汁酸合成の律速段階)

胆汁酸のホメオスタシスは、核内受容体 ファルネソイドX受容体 / farnesoid X receptor (FXR)によって厳密に規制されている。

通常の条件下では、胆汁酸による核内受容体 ファルネソイドX受容体 (FXR)の活性化によって、CYP7A1の発現は抑制され胆汁酸産生は低下する。

コレステロールレベルが高い場合、CYP7A1は肝臓X受容体(LXR)によってアップレギュレートされ、胆汁酸産生を増加させ幹細胞コレステロールレベルを低下させようとする。

Cholesterol 7 alpha-hydroxylase - Wikipedia

断食(PGC-1α活性)

Peroxisome Proliferator-activated Receptor-γ Coactivator-1α Activation of CYP7A1 during Food Restriction and Diabetes Is Still Inhibited by Small Heterodimer Partner
Cholesterol 7α-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the classic pathway of hepatic bile acid biosynthesis from cholesterol. During fasting a...

ビタミンD

ビタミンD受容体の活性化はCYP7A1を増加させコレステロールを低下させる。

Vitamin D receptor activation down-regulates the small heterodimer partner and increases CYP7A1 to lower cholesterol - PubMed
Activation of the VDR represses hepatic SHP to increase levels of mouse and human CYP7A1 and reduce cholesterol.

CYP8B1

主要な2つの胆汁酸ケノデオキシコール酸とコール酸のうちコール酸の合成にCYP8BAが必要となる。CYP8B1は、胆汁酸プールのケノデオキシコール酸とコール酸の比率を調節する。

Nuclear receptors in bile acid metabolism
Bile acids are signaling molecules that activate nuclear receptors, such as farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, and vit...

CYP11A1

シトクロムP450(CYP11A1)はミトコンドリアの膜内の酵素であり、LXRアゴニストの形成を触媒できる。

Differential regulation of the human CYP11A1 promoter in mouse brain and adrenals - PubMed
CYP11A1 encodes the first enzyme of steroid biosynthesis, cytochrome P450scc. The expression of CYP11A1 in the nervous system allows neurosteroids to be synthes...

CYP17A1

ステロイドホルモンの生合成ステップ

CYP17A1は、脳内のプレグネノロンをDHEAに変換する酵素。

図7

Upregulation of CYP17A1 by Sp1-mediated DNA demethylation confers temozolomide resistance through DHEA-mediated protection in glioma - Oncogenesis
Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroe...

rs743572

rs743572 - SNPedia
Dietary isoflavone intake, polymorphisms in the CYP17, CYP19, 17beta-HSD1, and SHBG genes, and risk of breast cancer in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians - PubMed
We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD1) and ...
Genetic polymorphisms of CYP17A1 in steroidogenesis pathway are associated with risk of progression to castration-resistant prostate cancer in Japanese men receiving androgen deprivation therapy - PubMed
The genetic backgrounds for CYP17A1 genes could influence the progression of prostate cancer to CRPC after androgen deprivation therapy.

CYP19A1

エストロゲンの形成(アロマターゼ酵素)

アンドロステンジオンは、17-ケトレダクターゼによってテストステロンに還元されるか、CYP19A1によってエストロンに芳香化される。

テストステロンまたはエストロンは、テストステロン還元(17-ケトレダクターゼ)またはエストロン芳香族化(CYP19A1)により、エストラジオール(17β-エストラジオール)に変換が可能。

 

エストロゲンと関連するCYP19A1遺伝子のrs3751592 A / G多型は中国漢民族のアルツハイマー病発症率と関連する。

The CYP19A1 rs3751592 variant confers susceptibility to Alzheimer disease in the Chinese Han population
The CYP19A1 enzyme (aromatase) encoded by the cytochrome P450 (CYP) 19A1 gene influences the final step in the biosynthesis of estrogen, which has been associat...

誘導剤

フォルスコリン

Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the human adrenocortical carcinoma cell line H295R - PubMed
A number of conditions related to sex-reversal in boys and men and precocious puberty in girls are caused by estrogen-secreting adrenal tumors. In these tumors,...

 

CYP24A1

CYP24A1は、ヒト脳でのビタミンDの異化に関与している。CYP24A1の活性化は、不活性であるカルシトロン酸を形成する。

Enzymes involved in the activation and inactivation of vitamin D - PubMed
Six cytochrome P450 (CYP) isoforms have been shown to hydroxylate vitamin D. Four of these, CYP27A1, CYP2R1, CYP3A4 and CYP2J3, are candidates for the enzyme vi...
Vitamin D and Alzheimer's Disease: Neurocognition to Therapeutics
Alzheimer's disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts ...
Calcitroic acid - Wikipedia

CYP24A1には多くの多型が特定されているが、この多型が及ぼす影響については殆ど知られていない。高カルシウム血症を引き起こすことが予想されている。

画像、イラストなどを保持する外部ファイル。オブジェクト名は13fig6.jpgです

Thematic Review Series: Fat-Soluble Vitamins: Vitamin D: Cytochrome P450-mediated metabolism of vitamin D
The vitamin D signal transduction system involves a series of cytochrome P450-containing sterol hydroxylases to generate and degrade the active hormone, 1α,25-d...

CYP27A1

ヒトのCYP27A1遺伝子変異は脳腱黄色腫症(CTX)として知られる胆汁酸と関連する障害をもたらす。これらは胆汁酸の不足によるビタミンDの吸収不良の結果であると考えれている。

Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis - PubMed
The sterol storage disorder cerebrotendinous xanthomatosis (CTX) is characterized by abnormal deposition of cholesterol and cholestanol in multiple tissues. Dep...

紫外線に曝されたマウスは、ビタミンDの合成を高めCYP27B1の発現が4倍増加した。炎症サイトカインであるIL-1βを5倍、IL-17を減少させることから、紫外線による抗炎症効果が示唆された。

高用量のビタミンD投与でもIL-17の減少は認められたが、有意な差ではなかった。単独よりもビタミンD摂取と紫外線曝露の両方によるビタミンD合成によって、有益な効果を得ること示唆される。

Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice
Reduced sunlight exposure has been associated with an increased incidence of Crohn’s disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) o...

CYP46A1

脳内コレステロール排出酵素 CYP46A1

CYP51A1

CYP51は、ラノステロールからコレステロール合成への中間体を生成する。

家族性アルツハイマー病におけるコレステロールレベルの上昇の根底にはCYP51発現の増加が示されている。

Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis - PubMed
Presenilins (PSs) are components of the gamma-secretase complex that mediates intramembranous cleavage of type I membrane proteins. We show that gamma-secretase...

CYP51の阻害剤(デブコナゾール)は、コレステロールレベルを低下させ、脂質ラフト関連APPの局在化を逆転させ大幅に低下することを示した。

Elevated cellular cholesterol in Familial Alzheimer’s presenilin 1 mutation is associated with lipid raft localization of β-amyloid precursor protein
Familial Alzheimer’s disease (FAD)-associated presenilin 1 (PS1) serves as a catalytic subunit of γ-secretase complex, which mediates the proteolytic liberation...

 

 

 

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