Brain-targeted proanthocyanidin metabolites for Alzheimer's disease treatment
Por:
Wang J., Ferruzzi M.G., Ho L., Blount J., Janle E.M., Gong B., Pan Y., Nagana Gowda G.A., Raftery D., Arrieta-Cruz I., Sharma V., Cooper B., Lobo J., Simon J.E., Zhang C., Cheng A., Qian X., Ono K., Teplow D.B., Pavlides C., Dixon R.A., Pasinetti G.M.
Publicada:
1 ene 2012
Categoría:
Neuroscience (miscellaneous)
Resumen:
While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as by limited knowledge regarding their bioavailability, metabolism, and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric forms. In this study, we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of 400 nM. Most importantly, we report for the first time that a biosynthetic epicatechin metabolite, 3'-O-methyl-epicatechin-5-O-ß-glucuronide (3'-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long-term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3'-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in AD and other forms of dementia. © 2012 the authors.
Filiaciones:
Wang J.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, United States
Ferruzzi M.G.:
Departments of Food Science and Foods and Nutrition, Purdue University, West Lafayette, IN 47907, United States
Ho L.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, United States
Blount J.:
Plant Biology Division, Samuel Roberts Noble Foundation, Ardmore, OK 73401, United States
Janle E.M.:
Departments of Food Science and Foods and Nutrition, Purdue University, West Lafayette, IN 47907, United States
Gong B.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Pan Y.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Nagana Gowda G.A.:
Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States
Raftery D.:
Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States
Arrieta-Cruz I.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Sharma V.:
Plant Biology Division, Samuel Roberts Noble Foundation, Ardmore, OK 73401, United States
Cooper B.:
Departments of Food Science and Foods and Nutrition, Purdue University, West Lafayette, IN 47907, United States
Lobo J.:
Departments of Food Science and Foods and Nutrition, Purdue University, West Lafayette, IN 47907, United States
Simon J.E.:
Department of Plant Biology and Plant Pathology, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, United States
Zhang C.:
Plant Biology Division, Samuel Roberts Noble Foundation, Ardmore, OK 73401, United States
Cheng A.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Qian X.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Ono K.:
Department of Neurology, David Geffen School of Medicine, and Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095, United States
Teplow D.B.:
Department of Neurology, David Geffen School of Medicine, and Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095, United States
Pavlides C.:
The Rockefeller University, New York, NY 10021, United States
Dixon R.A.:
Plant Biology Division, Samuel Roberts Noble Foundation, Ardmore, OK 73401, United States
Pasinetti G.M.:
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, United States
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, United States
Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY 10468, United States
All Open Access, Bronze
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