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Institute of Metabolic Disease at Baylor Research Institute
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Dr. Teodoro Bottiglieri, Ph.D.
Director of Neuropharmacology
Associate Professor of Biomedical Studies, Baylor University
Contact Information:
Phone: 214-820-4748
Education:
Ph.D. University of London 1992
Research Interests:
• Methylation and Homocysteine metabolism
• Risk factors for neurodegenerative disorders and vascular disease
• Role of gamma-hydroxybutyrate (GHB) on central nervous system function
Current Research:
The major focus of research in the Neuropharmacology laboratory is directed at understanding the role of methylation and carbon metabolism in the central nervous system (CNS). The transfer of one-carbon unit is an important biological process in the synthesis of methyl-tetrahydrofolate (MTHF) required in the synthesis of methionine and S-adenosylmethionine (SAMe). SAMe is a key regulatory molecule for numerous methylation dependent reactions involving DNA, proteins, phospholipids and neurotransmitter metabolism.
In addition one-carbon metabolism is intimately related with the regulation of homocysteine, a sulfur containing amino acid that has neurotoxic and atherosclerotic inducing properties. The Neuropharmacology laboratory collaborates with numerous medical centers and other institutes in the United States, investigating the clinical and metabolic relationships when methylation and one-carbon metabolism is altered due to genetic abnormalities, nutritional deficiencies and pharmacotherapies.
More specifically, current investigations that are in progress include studies in: children with inborn errors of one-carbon metabolism, Alzheimer’s disease, Parkinson’s disease, depression, HIV-infection and vascular disease.
Transgenic animal models are being studied in order to investigate the mechanism of toxicity of homocysteine in the CNS and in vascular endothelial cells. Another research focus of this laboratory is studying the neuropharmacological effects of gamma-hydroxybutyrate (GHB). The role of GHB on brain neurotransmitter metabolism and animal behavior is currently being investigated. This research is directed at finding treatments to prevent GHB toxicity related to drug abuse, and the inborn error of metabolism succinic semialdehyde dehydrogenase (SSADH) deficiency. The biochemical hallmark of SSADH deficiency is the accumulation of GHB in physiological fluids and tissues. An understanding of the pharmacological actions of GHB is crucial to finding effective therapies for this disorder.
Representative Publications:
Bottiglieri T. S-Adenosyl-L-methionine (SAMe): From the bench to the bedside— molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002 Nov; 76(5):1151S-7S.
Bolander-Gouaille C, Bottiglieri T. Homocysteine. Related Vitamins and Neuropsychiatric Disorders. Springer (Paris) 2003 ISBN: 2287043934. |
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