Shotgun lipidomics of liver and brain tissue of Alzheimer's disease model mice treated with acitretin.
Shotgun lipidomics of liver and brain tissue of Alzheimer's disease model mice treated with acitretin.
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DOI：
10.1038/s41598-021-94706-3
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发表时间：
2021-07-27
影响因子：
4.6
通讯作者：
Grimm MOW
中科院分区：
文献类型：
--
作者：
Lauer AA;Janitschke D;Dos Santos Guilherme M;Nguyen VTT;Bachmann CM;Qiao S;Schrul B;Boehm U;Grimm HS;Hartmann T;Endres K;Grimm MOW
阿尔茨海默病 (AD) 是一种非常常见的神经退行性疾病，其特征是淀粉样蛋白 - β (Aβ) 的积累。阿维A是一种类视黄醇衍生物，已被批准用于治疗寻常型银屑病，它可以增加非淀粉样变性淀粉样前体蛋白（APP）的加工，防止 Aβ 的产生并改善 AD 小鼠模型的认知能力。作为一种意想不到的副作用，阿维A可能导致高脂血症。在这里，我们分析了阿维A对 5xFAD 小鼠模型中脑和肝组织脂质组的影响。与文献一致，肝脏中甘油三酯增加，同时 PCaa、缩醛磷脂和酰基肉碱增加，而 SM 种类减少。在大脑中，这些效应部分增强或相似，但也相反。虽然 SM 和缩醛磷脂具有相似的作用，但 PCaa、TAG 和酰基肉碱在两种组织中都显示出相反的作用。我们的研究结果强调，应仔细监测治疗 AD 的潜在药物的脂质稳态，因为 APP 加工本身会调节脂质代谢，而药物治疗可能会导致进一步的意外变化。此外，应谨慎考虑从其他组织获得的结果推断脑脂质稳态的影响。就阿维A而言，脑缩醛磷脂的增加可能在AD治疗中显示出进一步的积极可能性，而其他结果，例如SM减少，表明需要对治疗的患者进行医疗监测。
Alzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients.
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DOI：
10.3945/ajcn.2009.27580
发表时间：
2009-08
期刊：
The American journal of clinical nutrition
影响因子：
--
作者：
Albanese E;Dangour AD;Uauy R;Acosta D;Guerra M;Guerra SS;Huang Y;Jacob KS;de Rodriguez JL;Noriega LH;Salas A;Sosa AL;Sousa RM;Williams J;Ferri CP;Prince MJ
通讯作者：
Prince MJ
DOI：
10.1097/nen.0000000000000116
发表时间：
2014-10-01
影响因子：
3.2
作者：
Cui, Yu;Liu, Xiuqin;Wu, Qunhong
通讯作者：
Wu, Qunhong
影响因子：
2.1
作者：
ARCHER, AG;NELSON, MC;BOGUMILL, GP
通讯作者：
BOGUMILL, GP
影响因子：
5.3
作者：
Green, Kim N.;Martinez-Coria, Hilda;LaFerla, Frank M.
通讯作者：
LaFerla, Frank M.
DOI：
10.1016/0167-4889(90)90108-p
发表时间：
1990-11-12
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CARILLET, V;MORLIERE, P;DUBERTRET, L
通讯作者：
DUBERTRET, L