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, 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 the premise that there are common final mediators of cell death signaling events that can be effectively targeted to treat neural disorders. This work if primarily focused on acute neuronal injury, such as that occurring during stroke, trauma and epilepsy. Nonetheless, the results obtained from these studies could have broader applications to more chronic conditions, such as Parkinson's and Alzheimer's disease. Over the last 20 years, the laboratory has investigated redox regulation of NMDA receptors, excitotoxicity, zinc-mediated neurotoxicity, and potassium channel facilitated forms of neuronal apoptosis, among other topics.

Sample publications:

Mandar A. Aras, Robert A. Saadi and Elias Aizenman. Zn2+ regulates Kv2.1 voltage-dependent gating and localization following ischemia. European Journal of Neuroscience 2009; 30:2250-2257.

Redman PT, Hartnett KA, Aras MA, Levitan ES, Aizenman E. Regulation of apoptotic potassium currents by coordinated zinc-dependent signaling. J Physiol. 2009 Sep 15;587(Pt 18):4393-404.

Aras MA, Hara H, Hartnett KA, Kandler K, Aizenman E. Protein kinase C regulation of neuronal zinc signaling mediates survival during preconditioning. J Neurochem. 2009 Jul;110(1):106-17.

Hershfinkel M, Kandler K, Knoch ME, Dagan-Rabin M, Aras MA, Abramovitch-Dahan C, Sekler I, Aizenman E. Intracellular zinc inhibits KCC2 transporter activity. Nat Neurosci. 2009 Jun;12(6):725-7.

Knoch ME, Hartnett KA, Hara H, Kandler K, Aizenman E. Microglia induce neurotoxicity via intraneuronal Zn(2+) release and a K(+) current surge. Glia. 2008 Jan 1;56(1):89-96.

Redman PT, He K, Hartnett KA, Jefferson BS, Hu L, Rosenberg PA, Levitan ES, Aizenman E. Apoptotic surge of potassium currents is mediated by p38 phosphorylation of Kv2.1. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3568-73.

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