title: Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease.
abstract: 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 I2(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-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.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Basurto-Islas
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Yunn Chyn
authors.initials: YC
authors.lastname: Tung
authors.affiliation: Signum Biosciences Inc, 133 Wall Street, Princeton, NJ 08540, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Fernandez
authors.affiliation: Signum Biosciences Inc, 133 Wall Street, Princeton, NJ 08540, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Voronkov
authors.affiliation: Signum Biosciences Inc, 133 Wall Street, Princeton, NJ 08540, USA.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Stock
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Signum Biosciences Inc, 133 Wall Street, Princeton, NJ 08540, USA; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
authors.forename: Jeffry B
authors.initials: JB
authors.lastname: Stock
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Electronic address: khalid.iqbal.ibr@gmail.com.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control*; D000818:Animals; D003069:Coffee / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D008745:Methylation / Q000187:drug effects; D018696:Neuroprotective Agents; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D003069:Coffee; D018696:Neuroprotective Agents; C000602511:eicosanoyl-5-hydroxytryptamide; D012701:Serotonin; C514014:Ppp2ca protein, rat; D054648:Protein Phosphatase 2
keywords: Adenoassociated virus vector serotype 1; Aβ; Coffee; Cognitive impairment; Eicosanoyl-5-hydroxytryptamide; Hyperphosphorylation of tau; Inhibitor-2 of protein phosphatase-2A; Methylation of protein phosphatase-2A; Protein phosphatase-2A; Rat model of sporadic Alzheimer’s disease; SET; Tau