INTRODUCTION The focus of the Neurodegeneration Laboratory is to determine the mechanisms of cell death and cell dysfunction which underlie a number of different disorders of the brain. These include both dementing illnesses and movement disorders, principally Alzheimer's disease, amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), Huntington's disease, Parkinson's disease and progressive supranuclear palsy (PSP), which are characterized by progressive neuronal degeneration in specific brain regions. In particular, we are interested in the roles that oxidative stress and abnormal energy metabolism in the brain play in all of these disorders, and in turn how these parameters are influenced by genetic mutations and predisposition, as well as extrinsic factors. By characterizing the events leading to neuronal loss in these disorders, the ultimate aim of these studies is to develop therapeutic strategies to both prevent disease onset and halt symptom progression. EXPERIMENTAL APPROACHES The experimental approaches used in the laboratory explore how cerebral function is altered in both affected human tissue and in transgenic mouse models of different neurodegenerative disorders. Techniques employed include HPLC to measure alterations in neurochemical levels ex vivo, notably energy metabolites and markers of free radical-mediated oxidative damage in cells; biochemical assays of metabolic enzyme activities; cell culture and cybrid approaches to measure mitochondrial and cell function in vitro; In vivo autoradiography to measure cerebral glucose metabolism; in vitro autoradiographic techniques to investigate neurotransmitter alterations; excitotoxic and mitochondrial toxin models of cell- and region-specific degeneration. MAJOR RESEARCH AREAS
- Measurement of markers for oxidative damage in body fluids pre-mortem, and in brain and spinal cord tissue post-mortem, in patients with neurodegenerative disorders.
- Determining genetic abnormalities in patient sub-populations.
- Assessment of alterations in different parameters of energy metabolism.
- Using transgenic mouse models of disease to characterize the development of functional and pathologic changes associated with the disease symptoms.
- Identifying, developing and testing potential therapeutic strategies in models of each of these neurodegenerative disorders.
RESEARCH TEAM The laboratory is led by Professor M. Flint Beal, M.D., who has attained international recognition as a leader in the area of cerebral neurochemistry in disease over twenty years of involvement in this field. Dr. Beal maintains an extremely active role in the laboratory's research endeavors. He is aided by a research team which currently boasts eight Ph.D. and M.D. researchers, whose areas of expertise encompass the neuroscience gamut, with seven full-time support staff.
