Our laboratory is interested in the various molecular mechanisms of selective neurodegeneration in motor neuron diseases such as amyotrophic lateral sclerosis. In particular, we are studying the basic biology of glutamate transporters and their role in neuronal degeneration. As an outgrowth of these studies, we investigate the basic synaptic and regulatory biology of glutamate transporters- thru the development of BAC-promoter reporter mice and cell surface trafficking methodologies. Other lab studies include the basic biology of glutamate transporters – the identification and cloning of interacting proteins which may be responsible for the cellular regulation of glutamate transporters: The targeted localization of transporters to perisynaptic regions and the subsequent cellular events that occur following glutamate transporter activation. These interacter proteins appear to regulate transport activity via G-protein-coupled events and membrane aggregation. Additional studies in the lab are focused on the role of mutant superoxide dismutase in motor neuron degeneration and various pre-clinical approaches to therapy including small molecule, gene therapy and stem cell biology driven approaches. Other diseases implicated in glutamate transporter subtype biology are being studied including epilepsy. Finally as a component to our motor neuron biology, core, models of motor axon regeneration regrowth are also being pursued.
- Lin C-L. G., Bristol L.A., Jin L., Dykes-Hoberg, M., Crawford, T., Rothstein, J.D., Aberrant RNA processing in a neurodegenerative disease: a common cause for loss of glutamate transport EAAT2 protein in sporadic amyotrophic lateral sclerosis. Neuron, 20, 589-602, 1998.
- Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18. Nature. 2001 Mar 1;410(6824):84-8.
- Jackson M, Song W, Liu MY, Jin L, Dykes-Hoberg M, Lin CI, Bowers WJ, Federoff HJ, Sternweis PC, Rothstein JD. Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature. 2001 Mar 1;410(6824):89-93.
- Jernia Llad C. Heggeli, E. Snyder and Jeffrey D. Rothstein. Neural stem cells are neurotrophic and neuroprotectant to motoneurons, in vitro and in vivo. Molecular Cellular Neuroscience, 2004, 27322-331
- Nicholas J. Maragakis, Mahendra S. Rao, Jeronia Llado, Douglas Kerr, Carol Coccia, and Jeffrey D. Rothstein. Glial Restricted Precursor Transplantation Protects Against Chronic Glutamate Neurotoxicity of Motor Neurons in Vitro. Glia, In press
- JD. Rothstein, S.Patel, M.R. Regan, C.Haenggeli, Y.H. Huang, D.E. Bergles, L. Jin, M. Dykes Hoberg, S. Vidensky, D.S. Chung, S. Vang Toan, L.I. Bruijn, Z. Su, P. Gupta, & P. B. Fisher. β Lactam Antibiotics Increase Neurotransmitter Glutamate Transporter Expression and Function by Gene Activation. Nature, 2005, In Press.