TY - JOUR
T1 - Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease
AU - Basurto-Islas, Gustavo
AU - Blanchard, Julie
AU - Tung, Yunn Chyn
AU - Fernandez, Jose R.
AU - Voronkov, Michael
AU - Stock, Maxwell
AU - Zhang, Sherry
AU - Stock, Jeffry B.
AU - Iqbal, Khalid
N1 - Funding Information:
We thank Dr Ezzat El-Akkad for help in the preparation of the figures and Ms Janet Murphy for secretarial assistance. Studies described in this article were supported in part by the New York State Office of People with Developmental Disabilities, National Institutes of Health grant AG019158 , and a research grant from (Signum Biosciences Inc , Princeton, NJ, USA).
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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 I2PP2A, 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-β 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.
AB - 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 I2PP2A, 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-β 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.
KW - Adenoassociated virus vector serotype 1
KW - Aβ
KW - Coffee
KW - Cognitive impairment
KW - Eicosanoyl-5-hydroxytryptamide
KW - Hyperphosphorylation of tau
KW - Inhibitor-2 of protein phosphatase-2A
KW - Methylation of protein phosphatase-2A
KW - Protein phosphatase-2A
KW - Rat model of sporadic Alzheimer's disease
KW - SET
KW - Tau
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U2 - 10.1016/j.neurobiolaging.2014.06.012
DO - 10.1016/j.neurobiolaging.2014.06.012
M3 - Article
C2 - 25034344
AN - SCOPUS:84911446629
SN - 0197-4580
VL - 35
SP - 2701
EP - 2712
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 12
ER -