The research is based on applying metabolic techniques (NMR spectroscopy) on tissue samples and tissues extracts from animal models for detection and characterization of biomarker, metabolic profiling and disease diagnosis. Primarily, we are interested in metabolic changes in the brain of the animal models of neurodegenerative diseases, such as Alzheimer’s disease.
Cholesterol: Side-chain oxidized oxysterols as metabolic regulators in liver and brain. 27-hydroxycholesterol (27-OH) and 24S-hydroxycholesterol (24S-OH) are major oxysterols in the circulation of man and mouse. 27-OH is formed by the enzyme sterol 27 hydroxylase (CYP27A1) a ubiquitously expressed enzyme. 24S-OH is formed by the enzyme cholesterol 24S-hydroxylase (CYP46A1). This enzyme is located almost exclusively in neuronal cells in the brain. These two oxysterols move in opposite directions across the blood-brain barrier. There is a constant flux of 24S-OH from the brain into the circulation and of 27- OH from the circulation into the brain.
Amyloid precursor protein (APP): Amyloid fibrils appear in the affected organs in a class of diseases called amyloid diseases (Sacchettini & Kelly, 2002). This class includes diseases that are major public health problems, such as Alzheimer’s diseases.
The project will be advanced by using NMR to better understand the complex structure of brain. The goals of using NMR are:
To characterize the lipid profile of brain by using NMR, such as fatty acids, phospholipids, cholesterol and possibly oxysterols. In addition, investigate the lipid profile in the amyloid precursor protein (APP) mouse, which is a model Alzheimer's disease
To study the effect of CYP27A1, Cyp27a1 on cholesterol homeostasis
To use solid state NMR (tissues) for better understanding of metabolic changes of brain (mouse models)