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Mano, Itzhak
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I study neuronal communication that uses the key excitatory neurotransmitter Glutamate, and the process of excitotoxicity, the neuronal cell death process that happen when the brain is flooded with too much glutamate. Excessive glutamate signaling triggers the neurodegeneration seen in prevalent neurodegenerative conditions such as stroke and diseases like ALS/Lau Gehrig’s disease. We understand very little about this form of neuronal cell death, and although the gradual progression of brain damage leaves a window of opportunity for clinical intervention, physicians have no effective therapies to treat it. Minority populations are especially at high risk, as African-Americans at 4 times more likely than Caucasians to suffer a stroke in middle age. I examine normal and pathological glutamatergic neurotransmission in the microscopic free-living nematode C. elegans, because of the strong genetic research tools available in this model system. The basic premise is that although we look very different from nematodes, we share a great similarity at the cellular and molecular levels. Therefore, if we understand basic processes of normal physiology and Glutamate-induced pathologies in nematodes, it might give us clues as to possible similar processes in people. Trained as a neuroscientist and experienced in molecular biology, electrophysiology and model-system genetics, I analyze structure-function relations in transport proteins to learn how excess Glutamate is removed from the nervous system. I use genetic tools to study what are the molecular steps that lead from Glutamate over-excitation to neurodegeneration, and I study the ability to interfere with evolutionary-conserved signaling pathways (such as cell stress or autophagy) to protect the nervous system from Glutamate-induced neurodegeneration.
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Mano, Itzhak