Grand Rounds: Wednesday, March 28, 2012

Fozia Mir, PhD, an Assistant Research Scientist at Tisch MS, presented a lecture on “Lipids in Multiple Sclerosis” Wednesday morning.  Lipids are very biologically active compounds that are highly susceptible to oxidative damage due to the presence of double bonds.  Oxidative stress can cause tissue injury, inflammation, and cell death and has been implicated in the pathogenesis of neurodegenerative diseases, including multiple sclerosis (MS).  The brain has a high lipid content which, combined with its high metabolism, low antioxidant levels, and high intracellular iron levels, makes it especially susceptible to oxidative damage.  In fact, prior research has documented changes in the profiles and absolute levels of bioactive lipids during development and disease processes.  However, it is unclear whether these changes are the cause or the result of neurodegeneration.

The main challenge in elucidating the role of oxidative stress in the development of neurodegenerative diseases, such as MS, is the current lack of biomarkers for oxidative stress.  Therefore, Dr. Mir’s research is focused on the following two objectives: 1) identifying products of lipid per-oxidation as biomarkers for oxidative stress and mitochondrial dysfunction, and 2) investigating the role of these products in the development of MS.  Dr. Mir’s group studies two markers of lipid per-oxidation in particular: isoprostanes and neuroketals.  Isoprostanes are the result of oxidation of arachidonic acid and are established markers of in vivo oxidative stress, whereas neuroketals are a recently reported oxidation product of docosahexaenoic acid.  Dr. Mir’s work has generated some promising results that demonstrate significant differences in isoprostane and neuroketal levels between MS subgroups and controls.  The results suggest that these compounds are present at significantly higher amounts in patients with progressive forms of MS and are potential biomarkers for oxidative stress in MS.