Washington University School of Medicine

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Joy Snider, MD, PhD

My laboratory is interested in exploring how neurons die in neurodegenerative disorders and stroke, with a specific focus on how abnormally folded proteins, such as amyloid b-peptide and polyglutamine-containing proteins, cause neuronal death. These proteins are involved in the pathogenesis of Alzheimer's disease and several dominantly inherited neurologic diseases, such as Huntington's disease, dentatopallidoluysian atrophy and several spinocerebellar ataxias. We initially focused on the ability of heat shock proteins or molecular chaperones to alter neuronal vulnerability to injury. More recently, we have examined the role of the proteasomal protein degradation system in neuronal injury. Most of our studies are done in primary neuronal cell culture, with an additional focus on neurons derived from murine embryonic stem cells.

Recently, we and others observed that neurons (and other cell types) can increase the function of the proteasomal protein degradation system in response to proteasome inhibition or oxidative stress. We are very interested in understanding how proteasome function is increased, and developing strategies to increase proteasome function as a potential therapeutic modality.

We are also interested in the mechanisms of neuronal death following proteasome inhibition or other injuries. Unlike neuronal death caused by over-stimulation of NMDA receptors (excitotoxic neuronal death), the neuronal death caused by inhibition of proteasome function is associated with a reduction, rather than an increase, in intracellular calcium levels ([Ca2+]i). If, as some studies suggest, proteasome function is impaired in the brains of patients with dementing disorders, these findings would suggest that treatments that reduce neuronal [Ca2+]i might exacerbate rather than reduce neuronal loss.

Medical Training

Dr. Snider received a B.A. in Biology from Northwestern University in 1979, then returned to Texas to the Medical Scientist Training Program at the University of Texas Southwestern Medical Center at Dallas, completing her M.D. and Ph.D. (in Biochemistry) in 1989. Dr. Snider completed the neurology residency program at Parkland Hospital in Dallas, Texas and joined the Neurology Department at Washington University in 1993. Dr. Snider is an Associate Professor in the Department of Neurology. Dr. Snider's clinical interests are in the diagnosis and treatment of patients with dementing disorders. She sees patients at the Memory Diagnostic Center and participates in research studies at the Washington University Alzheimer's Disease Research Center/Memory and Aging Project.

Selected Publications

Snider, B.J. (1998). Neuroprotective mechanisms of heat shock gene expression. The Neuroscientist 4:236-239.

Snider, B.J., Lobner, D., Yamada, K. and Choi, D.W. (1998) Conditioning Heat Stress Reduces Excitotoxic and Apoptotic Components of Oxygen-Glucose Deprivation-Induced Neuronal Death In Vitro. J. Neurochem. 77:120-129.

Snider, B.J. and Choi, D.W. (1996). Heat stress reduces glutamate toxicity in cultured neurons without hsp72 expression. Brain Research 729:273

McIver, S. R., Lee, C.-s., Lee, J.-M., Green, S. H., Sands, M. S., Snider, B. J. and Goldberg, M. P. (2005) In vivo gene transfer in murine oligodendrocytes using lentiviral vectors. J Neurosci Methods (in press).

Canzoniero, L.M., Snider, B.J. (2005) Calcium in Alzheimer's disease pathogenesis: too much, too little or in the wrong place? Journal of Alzheimer's Disease 8: in press.

Howard, M. J., Liu S., Schottler F., Snider, B. J., Jacquin, M. F. (2005) Transplantation of apoptosis-resistant embryonic stem cells into the injured rat spinal cord. Somatosens Mot Res 22:37-44.

Snider B. J., Norton J., Coats M. A., Chakraverty S., Hou C. E., Jervis R., Lendon C. L., Goate A. M., McKeel D. W., Jr. and Morris J. C. (2005) A novel presenilin 1 mutation (S170F) causing
Alzheimer's disease with Lewy bodies in the third decade of life. Arch Neurol in press.

Wei L., Cui L., Snider B. J., Rivkin M., Yu S. S., Lee C. S., Adams L. D., Gottlieb D. I., Johnson E. M., Jr., Yu S. P., Choi D. W. (2005) Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol Dis 19:183-193.

Lee, C. S., Tee, L.Y., Dusenbery, S., Takata, T., Golden, J. P., Pierchala, B.A., Gottlieb, D.I., Johnson, E.M., Jr., Choi, D.W. and Snider, B.J. (2005). Neurotrophin and GDNF Family Ligands Promote Survival and Alter Excitotoxic Vulnerability of Neurons derived from Murine Embryonic Stem Cells. Experimental Neurology 191: 65-76.

Lee, C. S., Tee, L.Y., Warmke, T., Cai, A.L., Vinjamoori, A. and Snider, B.J. (2004). A proteasomal stress response: pretreatment with proteasome inhibitors increases proteasome activity and reduces neuronal vulnerability to oxidative injury. J. Neurochemisty 91: 966-1006.

Canzoniero L.M., Babcock D.J., Gottron F.J., Grabb M.C., Manzerra P., Snider B.J., Choi D.W. (2004) Raising Intracellular Calcium Attenuates Neuronal Apoptosis Triggered by Staurosporine or Oxygen-Glucose Deprivation in the Presence of Glutamate Receptor Blockade. Neurobiol Dis 15:520-528.

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