Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:35

Article

Basurto-Islas, Gustavo¹  Blanchard, Julie¹  Tung, Yunn Chyn¹  Fernandez, Jose R.²  Voronkov, Michael²  Stock, Maxwell²  Zhang, Sherry³  Stock, Jeffry B.^2,3  Iqbal, Khalid¹ 

[1] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA

[2] Signum Biosci Inc, Princeton, NJ 08540 USA

[3] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

关键词: Protein phosphatase-2A;    Tau;    A beta;    Hyperphosphorylation of tau;    Rat model of sporadic Alzheimer's disease;    Coffee;    Eicosanoyl-5-hydroxytryptamide;    Cognitive impairment;    Methylation of protein phosphatase-2A;    Adenoassociated virus vector serotype 1;    Inhibitor-2 of protein phosphatase-2A;    SET;   

DOI  :  10.1016/j.neurobiolaging.2014.06.012

来源: Elsevier

【 摘 要 】

A minor component of coffee unrelated to caffeine, eicosanoyl-5-hydroxytryptamide (EHT), provides protection in a rat model for Alzheimer's disease (AD). In this model, viral expression of the phosphoprotein phosphatase 2A (PP2A) endogenous inhibitor, the I-2(PP2A), or SET protein in the brains of rats leads to several characteristic features of AD including cognitive impairment, tau hyperphosphorylation, and elevated levels of cytoplasmic amyloid-beta protein. Dietary supplementation with EHT for 6-12 months resulted in substantial amelioration of all these defects. The beneficial effects of EHT could be associated with its ability to increase PP2A activity by inhibiting the demethylation of its catalytic subunit PP2Ac. These findings raise the possibility that EHT may make a substantial contribution to the apparent neuroprotective benefits associated with coffee consumption as evidenced by numerous epidemiologic studies indicating that coffee drinkers have substantially lowered risk of developing AD. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

Free