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Research Newsletter-Spring/Summer 2008

OXYGEN CLUB OF CALIFORNIA ANNUAL MEETING


The Oxygen Club of California held its annual scientific conference, co-sponsored by LPI, in Santa Barbara, California, in mid-March. Oxidants and Antioxidants in Biology featured 37 presentations in six sessions: "Age-related Metabolic Pathways, Mitochondrial Nutrients, and Neurodegeneration," "Choline, Metals, Amino Acids, and Lipophilic Micronutrients in Brain Health and Function," "Flavonoids in Cell Signaling and Neuronal Function," "Oxidative Stress and Thiol Redox Circuits in Cell Function," "Lipoic Acid in Cell Signaling and Transcription," and "Clinical Studies on Lipoic Acid."

William Pardridge (UCLA) and Bert Sakmann (Max- Planck-Institute for Medical Research), winner of the 1991 Nobel Prize in Medicine or Physiology for "discoveries concerning the function of single ion channels in cells," gave the keynote lectures. Pardridge discussed the types of molecules that cross the blood-brain barrier (BBB). Only small lipid-soluble molecules diffuse across the BBB, but larger water-soluble molecules cross via three mechanisms. One of these, the receptor-mediated transport system, may be used to allow Trojan horse molecules to deliver metabolites or drugs to the brain. Sakmann described rat experiments in which energy expenditures in extremely small regions of the brain can be measured and correlated with specific actions, such as a whisker twitch, and concluded, "thoughts need food."

Several presentations focused on abnormal molecular events that characterize Alzheimer's disease. Based on its attenuation of inflammation in cell culture studies, 600 mg/day of alpha-lipoic acid were given to a small group of Alzheimer's patients for four years. While no significant effect on cognitive decline was found in moderate to severe Alzheimer's patients, those with early dementia exhibited less deterioration in cognitive function. In animal experiments, antioxidant treatment lowered oxidative stress caused by amyloid beta-peptide formation in the brain. Amyloid beta-peptide and neurofibrillary tangles are pathological abnormalities in the brain associated with Alzheimer's disease. Novel estrogen-like molecules and genistein from soy have been tested in vitro for their neuroprotective properties and may help prevent cognitive decline associated with estrogen deficiency. Additionally, pomegranate juice fed to mice used as a model of Alzheimer's disease reduced the formation of amyloid beta-peptide by about 50%, which was associated with improved cognitive and physical performance.


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Flavonoids in blueberries and another flavonoid in strawberries called fisetin affect cell signaling pathways and improve neuronal function in the brain. However, flavonoids, such as tea catechins, are poorly absorbed into the bloodstream and extensively and rapidly metabolized. Their metabolites have not been detected in cerebrospinal fluid, although the effects of supplementation on brain function have been repeatedly demonstrated. Flavonoids in tea and pomegranates have also been shown to inhibit the development of prostate cancer.

Alpha-lipoic acid, an effective mitochondrial antioxidant, has been used to treat diabetic neuropathy, probably by modulating cell-signaling pathways and reducing advanced glycation end products. Lipoic acid has also been found to prevent cardiomyopathy in mice. Lipoic acid fed to old rats protects them from toxicological insults by increasing the synthesis of glutathione, an important endogenous antioxidant involved in detoxification. In old rats, lipoic acid elevates the nuclear levels of the transcription factor, Nrf2, that regulates the synthesis of glutathione. When fed to old rats in combination with acetyl-L-carnitine, a non-protein amino acid, lipoic acid improves mitochondrial function, resulting in reversal of age-related declines in cognitive function and physical activity. The combination has also been found to reduce hypertension in people and to lower markers of inflammation in patients with sickle-cell anemia.

About 90 posters were also presented on topics ranging from the growth inhibition by vitamin C of human tumors implanted in mice to the relaxation of arteries by kynurenine, which is derived from the amino acid tryptophan.

Awards were given to Drs. Enrique Cadenas, Klaus Kraemer, and Steven Zeisel. LPI Principal Investigator Dr. Tory Hagen won the Outstanding Investigator Award. Additionally, Young Investigator Awards were presented to Drs. Sabine Augustin, Philip Lam, and Kit Tong.


Last updated June 2008