Amyotrophic Lateral Sclerosis (ALS) is a relatively rare neurodegenerative disorder that is fatal 2-4 years after the onset of the disease. Population studies are being done in order to help reveal candidates for further studies of disease etiology, disease progression, as well as to further understand racial and ethnic variations....
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by neuromuscular junction decay, motor neuron death, progressive paralysis, and eventually death of the individual, usually by respiratory failure. Oxidative stress is a prominent hallmark of the disease and is often accompanied and exacerbated by mitochondrial dysfunction and neuroinflammation. This...
Oxygen derived radicals are involved in many aspects of life from aging and cell signaling to disease states as diverse as heart disease, diabetes, neurodegeneration and inflammation. Therefore, understanding the function of antioxidant defense proteins and the effects of oxygen derived radicals on protein function is essential to elucidate the...
Altogether, this dissertation highlights the value of mass spectrometry-based analysis of intact proteins for solving problems related to understanding disease mechanisms and developing new therapeutics.
Mutations to the antioxidant enzyme Cu, Zn Superoxide Dismutase (SOD1) perturb protein structure in vivo to cause 2-5% of amyotrophic lateral sclerosis (ALS) cases. Metal-deficient...
Mutations to superoxide dismutase were the first proven cause of Lou
Gehrig’s disease (amyotrophic lateral sclerosis; ALS) implicating superoxide in
the selective death of motor neurons that characterizes ALS. Nitric oxide
competes effectively with superoxide dismutase for superoxide to form the
powerful oxidant peroxynitrite. Endogenous formation of peroxynitrite can kill...
People turn to mass spectrometry to answer some of life’s most important questions. From carbon dating of archeological finds to newborn blood screening tests, mass spectrometry allows us to measure molecules which helps advance our knowledge of life and the world we live in. One area of mass spectrometry that...
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive degeneration of motor neurons. Dominantly-inherited mutations to the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) cause 3-6% of all ALS cases. The complete mechanism behind the toxicity of mutant SOD1 remains unclear, although significant evidence points to aberrant or...
Presentation entitled : The Challenge of Finding Where SOD Gets Zinc: Identifying Novel Techniques to Recombinantly Express Metallothionein / by Nick B. West, Joseph Beckman and Daniel Sudakin
This thesis includes three studies involving different aspects of modeling protein structure. The first study illustrates the levels of insight available from atomic-resolution protein structures. The second study derives general trends of protein geometry from atomic-resolution structures and shows their implications for modeling. The third study creates a model of...
Ceramides are a group of lipids in the sphingolipid family that are potent cell signaling molecules. Elevations in ceramide levels above the norm generally lead to apoptosis. Evidence from in vitro studies suggests that accumulation of ceramides within mitochondria leads to dysfunction of the mitochondria. This includes inhibition of the...