Research in Dr. Aizenmans laboratory is directed towards investigating cellular signaling processes leading to neuronal cell death.
Injurious processes in the brain lead to the activation of signaling cascades that eventually result in the demise of neurons. In Dr. Aizenman's laboratory, cellular pathways leading to cell death are being molecularly dissected in order to provide novel therapeutic targets to treat neurodegenerative disorders. This laboratory works on potential final common mediators of cell death signaling events that can be effectively targeted to treat neuronal disorders. This work is primarily focused on acute neuronal injury, such as stroke, although the results from these studies could have broader applications to more chronic neurodegenerative conditions, such as Parkinson's disease, ALS and Alzheimer's disease. Over the last several years, the laboratory has investigated redox and photic regulation of NMDA receptors, excitotoxicity, dopamine oxidation pathways, zinc-mediated neurotoxicity, and potassium channel facilitated forms of neuronal apoptosis, among other topics.
Recent key publications:
Hershfinkel, M., D. Ford, S. Kelleher and E. Aizenman. Seashells by the zinc shore: a meeting report of the international society for zinc biology, Asilomar, CA 2014. Metallomics 2015 (in press; DOI: 10.1039/c5mt90029h).
He, K., M.C. MCord, K.A. Hartnett and E. Aizenman. Regulation of pro-apoptotic phosphorylation of Kv2.1 K+ channels. PLoS One 2015; 10(6):e0129498.
Gilad, D., S. Shorer, M. Ketzef, A. Friedman, I. Sekler, E. Aizenman and M. Hershfinkel. Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures. Neurobiology of Disease (2015; Epub ahead of print).
Hara, H. and E. Aizenman. Oxidative stress and neuronal zinc signaling. In: Zinc Signals in Cellular Functions and Disorders. Fukada, T. and T. Kambe, eds. Springer Japan 2014; Chapter 4, pp. 55-87.
McCord, M.C., P.H. Kullmann, K. He, K.A. Hartnett, J.P. Horn, I. Lotan and E. Aizenman. Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+ currents. Journal of Physiology 2014; 592:3511-3521.
McCord, M.C. and E. Aizenman. The role of intracellular zinc release in aging, oxidative stress, and Alzheimer's disease. Frontiers in Aging Neuroscience 2014; doi:10.3389/fnagi.2014.00077
Shah, N.H., A.J. Schulien, K. Clemens, T.D. Aizenman, T.M. Hageman, Z.P. Wills and E. Aizenman. Cyclin E1 regulates Kv2.1 channel phospohorylation and localization in neuronal ischemia. Journal of Neuroscience 2014; 34:4326-4331.
Shah, N.H. and E. Aizenman. Voltage-gated potassium channels at the crossroads of neuronal function, ischemic tolerance, and neurodegeneration. Translational Stroke Research 2014; 5:38-58.
McCord, M.C. and E. Aizenman. Convergent calcium and zinc signaling regulates apoptotic Kv2.1 potassium currents. Proceedings of the National Academy of Sciences (USA) 2013; 110:13988-13993.
Perez-Rosello, T., C.T. Anderson, F.J. Schopfer, Y. Zhao, D. Gilad, S.R. Salvatore, B.A. Freeman, M. Hershfinkel, E. Aizenman and T. Tzounopoulos. Synaptic zinc inhibits neurotransmitter release by promoting endocannabinoid synthesis. Journal of Neuroscience 2013; 33:9259-9272.
Norris, C.A., K. He, M.G. Springer, K.A. Hartnett, J.P. Horn and E. Aizenman. Regulation of neuronal pro-apoptotic potassium currents by the hepatitis C virus non-structural protein 5A. Journal of Neuroscience 2012; 32: 8865-8870.
Saadi, R.A., K. He, K.A. Hartnett, K. Kandler, M. Hershfinkel and E. Aizenman. SNARE-dependent upregulation of KCC2 activity following metabotropic zinc receptor activation in rat cortical neurons in vitro. Neuroscience 2012; 210: 38-46.
Sensi, S.L., Paoletti, P., Koh, J.-Y., Aizenman, E., Bush, A.I. and Hershfinkel, M. The neurophysiology and pathology of brain zinc. Journal of Neuroscience 2011; 31: 16076-16085.
Chorin, E., O. Vinograd, I. Fleidervish, D. Gilad, S. Hermann, I. Sekler, E. Aizenman and M. Hershfinkel. Upregulation of KCC2 activity by zinc-mediated neurotransmission via the mZnR/GPR39 receptor. Journal of Neuroscience 2011; 31:12916-12926.
Aras, M.A. and E. Aizenman. Redox regulation of intracellular zinc: Molecular signaling in the life and death of neurons. Antioxidants and Redox Signaling 2011; 15: 2249-2262.
He, K. and E. Aizenman. ERK signaling leads to mitochondrial dysfunction in extracellular zinc-induced neurotoxicity. Journal of Neurochemistry 2010; 114:452-461.
Hershfinkel, M., K. Kandler, M.E. Knoch, M. Dagan-Rabin, M.A. Aras, C. Abramovitch-Dahan, I. Sekler and E. Aizenman. Intracellular zinc inhibits KCC2 transporter activity. Nature Neuroscience 2009; 12:725-727.