University of Chicago Dr Horwitz' laboratory is interested in research related to neurotoxicology and neurodegeneration. One research goal is to understand the effects of long-term ethanol exposure on signal transduction in neuronal systems. Long-term ethanol down regulates phospholipase D activity but does not appear to affect the phospholipase C specific for inositol containing phospholipids. Different mechanisms of activation account for the differential effects of ethanol. For example, the activation of phospholipase D is mediated by tyrosine kinases, whereas the activation of phospholipase C is mediated by G-proteins.
Current research is focused on the regulatory role of phosphorylation.
Another research goal is to understand the role of free radicals in the etiology of Parkinson s disease and other neurodegenerative diseases. We are particularly interested in peroxynitrite mediated toxicity to catecholamine containing cells. Peroxynitrite is an oxygen reactive molecule that is formed by the near diffusion limited reaction of superoxide with nitric oxide. These metabolites are found at high concentrations in the substantia nigra, the area that degenerates in Parkinson s. Initial studies suggest that peroxynitrite inhibits tyrosine hydroxylase by nitration of tyrosine residues.