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Mark A. LovellAssociate Professor of Chemistry
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Increasing evidence suggests alterations in zinc (Zn) homeostasis may contribute to neurodegeneration observed in the pathogenesis of Alzheimer’s disease (AD). Current studies from our laboratory show there are significant alterations in proteins responsible for the transport and sequestration of Zn (ZnT proteins) that occur early in the progression of AD. Our data also suggest that alterations of ZnT proteins and the corresponding disruption of Zn balance can contribute to increased oxidative damage in AD. Our current research centers around the use of Western blot analysis, immunohistochemistry/laser confocal microscopy and genetic manipulation of neuronal cell lines to study alterations of ZnT proteins. We also use GC-MS, HPLC, cell culture techniques and transgenic animals to correlate altered ZnT levels and markers of oxidative damage including oxidized DNA adducts and neurotoxic by-products of lipid peroxidation (4-hydroxynonenal, acrolein). Additional studies include analysis of by-products of RNA oxidation in the progression of AD and evaluation of the biological impact of RNA oxidation using primary rat cortical neuron cultures.  Representative composite of cells from a subject with mild cognitive impairment (MCI) double labeled for ZnT-6 (A; green) and MC-1 (B; red), a marker of early neurofibrillary tangle formation. Figure C is a merged image. Note considerable overlap between ZnT-6 and MC-1 immunostaining. Scale bar = 50 µm. Visit the Sanders-Brown Center on Aging and its Alzheimer's Disease Research Center.
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