Joseph S. Beckman
Joseph S. Beckman
A major research project in my laboratory is aimed at understanding how oxidative stress, superoxide dismutase, and zinc are involved in Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). ALS is a dreadful disease caused by the unexplained death of motor neurons that control the movement of all voluntary muscles. We have only about 500,000 motor neurons at birth that cannot be replaced. One known cause of ALS is mutations in the antioxidant enzyme copper/zinc superoxide dismutase that results in the loss of zinc binding and then copper binding from the enzyme, making it toxic to motor neurons. One of our major projects in the laboratory focuses on delivering copper to the enzyme to refold it properly. To this end, we are using a copper compound called Cu-ATSM, a form of copper that accumulates in hypoxic tissue, to deliver copper. Not only does Cu-ATSM appear to work in laboratory animals, it has recently facilitated linical trials on its therapies on humans with ALS.
- Amyotrophic Lateral Sclerosis (ALS)
College Strategic Research AreasBiomedical Science
- Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J. Neuroinflammation (2016) 13:177.
- Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD. Neurobiol Dis (2016) 89:1-9.
- Oral treatment with CuII(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci (2014) 34:8021-8031.
- Phenotypic transition of microglia into astrocyte-like cells associated with disease onset in a model of inherited ALS. Front Cell Neurosci (2013) 7:274.
- Nitration of Hsp90 induces cell death. Proc Natl Acad Sci USA (2013) 110:E1102-E1111.