Cellular & molecular mechanisms of neurodegeneration
Research in Dr. Aizenman's laboratory is directed towards investigating cellular signaling processes leading to neuronal cell death.
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, cellular pathways leading to cell death are molecularly 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 several 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.
Recent publications:Regulation of pro-apoptotic phosphorylation of Kv2.1 K+ channels.
He K, McCord MC, Hartnett KA, Aizenman E.
PLoS One 2015 Jun 26; 10(6):e0129498.
Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures.
Gilad D, Shorer S, Ketzef M, Friedman A, Sekler I, Aizenman E, Hershfinkel M.
Neurobiol Disease (2015; Epub ahead of print)
Oxidative stress and neuronal zinc signaling.
Hara H, Aizenman E.
In: Zinc Signals in Cellular Functions and Disorders. Fukada T, Kambe T (eds.) Springer, Japan, 2014; Chapter 4, pp. 55-87.
Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+ currents.
McCord MC, Kullmann PH, He K, Hartnett KA, Horn JP, Lotan I, Aizenman E.
J Physiol. 2014 592:3511-3521
The role of intracellular zinc release in aging, oxidative stress, and Alzheimer's disease.
McCord MC, Aizenman E.
Front Aging Neurosci. 2014 Apr 17;6:77.
Cyclin E1 regulates Kv2.1 channel phospohorylation and localization in neuronal ischemia.
Shah NH, Schullen AJ, Clemens K, Aizenman TD, Hageman TM, Wills ZP, Aizenman E.
J Neurosci. 2014 Mar 19;34(12):4326-31.
Voltage-Gated Potassium Channels at the Crossroads of Neuronal Function, Ischemic Tolerance, and Neurodegeneration.
Shah NH, Aizenman E.
Transl Stroke Res. 2014 Feb;5(1):38-58.
Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents.
McCord MC, Aizenman E.
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13988-93.
Synaptic Zn2+ inhibits neurotransmitter release by promoting endocannabinoid synthesis.
Perez-Rosello T, Anderson CT, Schopfer FJ, Zhao Y, Gilad D, Salvatore SR, Freeman BA, Hershfinkel M, Aizenman E, Tzounopoulos T.
J Neurosci. 2013 May 29;33(22):9259-72.
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of Pittsburgh Department of Neurobiology