Acute and chronic 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, molecular pathways leading to cell death are being carefully dissected in order to provide novel therapeutic targets to treat neurodegenerative disorders. This laboratory works on potential common final mediators of cell death signaling events that can be effectively targeted to treat neural disorders. This work is primarily focused on acute neuronal injury, such as stroke, although the results obtained from these studies could have broader applications to more chronic neurodegenerative conditions. Over the last 22 years, the laboratory has investigated redox and photic regulation of NMDA receptors, excitotoxicity, dopamine oxidation pathways, zinc-mediated neurotoxicity, and Kv2.1 potassium channel facilitated forms of neuronal apoptosis, among other topics.
Yeh, C., Schulien, A., Molyneaux, B., Aizenman, E. Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection. International Journal of Molecular Sciences. 2020 Aug 25;21(17):E6107. doi: 10.3390/ijms21176107.
Aizenman, E., R.H. Loring, I.J. Reynolds and P.A. Rosenberg. The redox biology of excitotoxic processes: the NMDA receptor, TOPA quinone, and the oxidative liberation of intracellular zinc. Frontiers in Neuroscience - Special Issue: Excitotoxicity Turns 50. 2020, 14:778, DOI: 10.3389/fnins.2020.00778.
Schulien, A.J., C.-Y Yeh, B.N. Orange, O.J. Pav, M.P. Hopkins, A. Moutal, R. Khanna, D. Sun, J.A. Justice* and E. Aizenman.* Targeted-disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels. Science Advances 01 Jul 2020: Vol. 6, no. 27, eaaz8110; DOI: 10.1126/sciadv.aaz8110 .
Krall, R.F., A. Moutal, M.B. Phillips, H. Asraf, J.W. Johnson, R. Khanna, M. Hershfinkel, E. Aizenman* and T. Tzounopoulos.* Synaptic zinc inhibition of NMDA receptors depends on the association of GluN2A with the zinc transporter ZnT1. Science Advances 03 Jul 2020: Vol. 6, no. 27, eabb1515; DOI: 10.1126/sciadv.abb1515
Aizenman E. Zinc signaling in the life and death of neurons. In: Zinc Signals in Cellular Functions and Disorders. Second Edition. Fukada, T. and T. Kambe, eds. Springer, 2019, Chapter 9; pp. 165-185.
Yeh, C.-Y., Z. Ye, A. Moutal, S. Gaur, A.M. Henton, S. Kouvaros, J.L. Saloman, K.A. Hartnett-Scott, T. Tzounopoulos, R. Khanna, E. Aizenman* and C.J. Camacho.* Defining the Kv2.1-syntaxin interaction identifies a first-in-class small molecule neuroprotectant. Proceedings of the National Academy of Sciences (USA) 2019; 116:15696-15705.
Justice, J.A., D.T. Manjooran, C.-Y. Yeh, K.A. Hartnett-Scott, A.J. Schulien, G.J. Kosobucki, S. Mammen, M.J. Palladino and E. Aizenman. Molecular neuroprotection induced by zinc-dependent expression of hepatitis C-derived protein NS5A targeting Kv2.1 potassium channels. Journal of Pharmacology and Experimental Therapeutics 2018; 367:348-355.
Yeh, C.-Y., A.M. Bulas, A. Moutal, J.L. Saloman, K.A. Hartnett, C.T. Anderson, T. Tzounopoulos, D. Sun, R. Khanna and E. Aizenman. Targeting a potassium channel/syntaxin interaction ameliorates cell death in ischemic stroke. Journal of Neuroscience 2017; 37:5648-5658.