Increasing evidence has strongly suggested a role for inflammatory responses in the brain in the development of several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and the AIDS dementia complex. Activation of glial cells in the brain, a process called """"""""reactive gliosis"""""""", is frequently observed. Activated glial cells, astrocytes and microglia, synthesize and secrete a large number of proinflammatory and cytotoxic factors that may have a crucial impact on the repair of neuronal damage or the production of further neuronal injury. In general, reactive astrocytes are hypothesized to function in a neuroprotective capacity by producing trophic factors that facilitate neuronal repair, whereas reactive microglia synthesize proinflammatory cytokines and free radicals that result in neurotoxicity. Reactive glial cells are also capable of producing lipid mediators which participate in the regulation of the inflammatory and degenerative processes. Arachidonic acid (AA), one of these mediators, is rapidly converted by cyclooxygenase (COX) to biologically active prostaglandins and thromboxanes or, alternatively, to leukotrienes and hydroxy fatty acids by lipoxygenase (LOX). Although the activity of AA-metabolizing enzymes, especially COX, is clearly associated with the inflammatory process, the study of the contribution of the metabolites of these enzymes to the inflammation-mediated neurodegeneration in the brain is just beginning. Using cell cultures and experimental animal models, this study proposes to examine the role of COX enzymes in the pathogenesis of Parkinson's disease and cerebral ischemia. The results from these experiments will help to design effective therapeutic agents for the treatment of these neurological disorders.
| Feng, Z-H; Wang, T-G; Li, D-D et al. (2002) Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra. Neurosci Lett 329:354-8 |
