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.
Bogdanovic M, Asraf H, Gottesman N, Sekler I, Aizenman E, Hershfinkel M. The ZIP3 zinc transporter is localized to mossy fiber terminals and is required for kainate-induced degeneration of CA3 neurons. Journal of Neuroscience 2022 Feb 14:JN-RM-0908-21. doi: 10.1523/JNEUROSCI.0908-21.2022. Epub ahead of print. PMID: 35169020.
Asraf H, Bogdanovic M, Gottesman N, Sekler I, Aizenman E, Hershfinkel M. SNAP23 regulates KCC2 membrane insertion and activity following mZnR/GPR39 activation in hippocampalneurons. iScience. 2022 Jan 7;25(2):103751. doi: 10.1016/j.isci.2022.103751. PMID: 35118363; PMCID: PMC8800107.
Gottesman N, Asraf H, Bogdanovic M, Sekler I, Tzounopoulos T, Aizenman E, Hershfinkel M. ZnT1 is a neuronal Zn2+/Ca2+ exchanger. Cell Calcium. 2022 Jan;101:102505. doi: 10.1016/j.ceca.2021.102505. Epub 2021 Nov 23. PMID: 34871934.
Gale JR, Kosobucki GJ, Hartnett-Scott KA, Aizenman E. Imprecision in Precision Medicine: Differential Response of a Disease-Linked GluN2A Mutant to NMDA Channel Blockers. Front Pharmacol. 2021 Oct 28;12:773455. doi: 10.3389/fphar.2021.773455. PMID: 34776984; PMCID: PMC8581401.
Kowalczyk A, Gbadamosi O, Kolor K, Sosa J, Andrzejczuk L, Gibson G, St Croix C, Chikina M, Aizenman E, Clark N, Kiselyov K. Evolutionary rate covariation identifies SLC30A9 (ZnT9) as a mitochondrial zinc transporter. Biochem J. 2021 Sep 17;478(17):3205-3220. doi: 10.1042/BCJ20210342. PMID: 34397090.
Liu HY, Gale JR, Reynolds IJ, Weiss JH, Aizenman E. The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction. Biomedicines. 2021 Apr 29;9(5):489. doi: 10.3390/biomedicines9050489.
Krall RF, Tzounopoulos T, Aizenman E. The Function and Regulation of Zinc in the Brain. Neuroscience. 2021 Mar 1;457:235-258. doi: 10.1016/j.neuroscience.2021.01.010.
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, January 2020, Chapter 9; pp. 165-185.