Title: Pharmacologic Strategies for Suppression of Lipid Peroxidation in Neurodegeneration
Volume: 1
Issue: 2
Author(s): K. S. Montine, D. Milatovic, M. Doherty, J. D. Morrow and T. J. Montine
Affiliation:
Keywords:
lipid peroxidation, neurodegeneration, free radical-mediated injury, huntingtons disease, human immunodeficiency virus-associated dementia
Abstract: Lipid peroxidation is one of the major outcomes of free radical-mediated injury to tissue that directly damages membranes and generates a number of secondary biologically active products. This occurs through fragmentation and rearrangement of oxygenated fatty acids that act via modification of macromolecules and activation of cell surface receptors. Numerous studies have demonstrated regionally increased brain lipid peroxidation in patients who have suffered acute brain injury from trauma or cerebrovascular disease as well as patients with protracted neurodegenerative diseases such as Alzheimers disease, Parkinsons disease, Huntingtons disease, and human immunodeficiency virus-associated dementia. Recent studies have progressed from determining biomarkers of lipid peroxidation in tissue obtained post mortem to measuring levels in body fluids from living patients early in the course of disease. Elevated biomarkers of lipid peroxidation early in disease establish it as a potential therapeutic target and provide a novel method for following disease progression and response to therapy. Strategies for limiting the deleterious effects of lipid peroxidation include pharmacologic intervention at several points. We will present recent results from our laboratory on some of these therapeutic targets. Continuing development of pharmacologic targets and therapeutic interventions in experimental models of neurodegenerative diseases that include oxidative damage to brain may lead to effective interventions for this facet of neurodegeneration.
