I thought some might find this of interest - couldn't figure out where to put it, so here it is: http://www.jneurosci.org/content/18/2/687.short Mitochondrial Manganese Superoxide Dismutase Prevents Neural Apoptosis and Reduces Ischemic Brain Injury: Suppression of Peroxynitrite Production, Lipid Peroxidation, and Mitochondrial Dysfunction Jeffrey N. Keller1,2, Mark S. Kindy2,3, Fredrick W. Holtsberg1, Daret K. St. Clair4, Hsiu-Chuan Yen4, Arriane Germeyer2, Sheldon M. Steiner1, Annadora J. Bruce-Keller2, James B. Hutchins6, and Mark P. Mattson2,5 Abstract Oxidative stress is implicated in neuronal apoptosis that occurs in physiological settings and in neurodegenerative disorders. Superoxide anion radical, produced during mitochondrial respiration, is involved in the generation of several potentially damaging reactive oxygen species including peroxynitrite. To examine directly the role of superoxide and peroxynitrite in neuronal apoptosis, we generated neural cell lines and transgenic mice that overexpress human mitochondrial manganese superoxide dismutase (MnSOD). In cultured pheochromocytoma PC6 cells, overexpression of mitochondria-localized MnSOD prevented apoptosis induced by Fe2+, amyloid ?-peptide (A?), and nitric oxide-generating agents. Accumulations of peroxynitrite, nitrated proteins, and the membrane lipid peroxidation product 4-hydroxynonenal (HNE) after exposure to the apoptotic insults were markedly attenuated in cells expressing MnSOD. Glutathione peroxidase activity levels were increased in cells overexpressing MnSOD, suggesting a compensatory response to increased H2O2 levels. The peroxynitrite scavenger uric acid and the antioxidants propyl gallate and glutathione prevented apoptosis induced by each apoptotic insult, suggesting central roles for peroxynitrite and membrane lipid peroxidation in oxidative stress-induced apoptosis. Apoptotic insults decreased mitochondrial transmembrane potential and energy charge in control cells but not in cells overexpressing MnSOD, and cyclosporin A and caspase inhibitors protected cells against apoptosis, demonstrating roles for mitochondrial alterations and caspase activation in the apoptotic process. Membrane lipid peroxidation, protein nitration, and neuronal death after focal cerebral ischemia were significantly reduced in transgenic mice overexpressing human MnSOD. The data suggest that mitochondrial superoxide accumulation and consequent peroxynitrite production and mitochondrial dysfunction play pivotal roles in neuronal apoptosis induced by diverse insults in cell culture and in vivo. ----------- Has anyone tried supplementing with MnSOD? Also note that uric acid is a peroxynitrite scavanger, which may be why uric acid seems to protect against multiple sclerosis. I think pursuing anything the deals with lipid peroxidation will help mitochondrial dysfunction. I can't really reasearch it now because w/o a mouse I am slower than if I was dargging a railroad tie behind me. Please don't get riled about the term "mitochondrial dysfunction" _ I say just use the search string the researchers use and mine their info and go on. The object is to gain knowledge, IMHO.