Ph.D. University of Kentucky, 1992
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.
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Analytical and Biological Chemistry
- M.A. Bradley-Whitman and M.A. Lovell*, Mass spectrometry and studies of nucleic acid oxidation in neurodegenerative diseases”, (Invited Review), J. Anal. Bioanal. Chem, In press, (2013).
- M. A. Bradley-Whitman, M. D. Timmons, T. L. Beckett, M. P. Murphy, B. C. Lynn, and M.A. Lovell* “Nucleic acid oxidation: an early feature of Alzheimer’s disease” J. Neurochem., In press, (2013).
- M.D. Timmons, M.A. Bradley, M.A. Lovell and B.C. Lynn, “Changes in the mitochondrial lipidome in the progression of Alzheimer’s disease”, J. Lipid Res. In press, (2013).
- M.A. Bradley and M.A. Lovell* “Epigenetic changes in the brain in the progression of Alzheimer’s disease”, Invited article, Mech. Ageing Dev. In press, (2013).
- M.A. Lovell*, M.A. Bradley and S.X. Fister, “4-Hydroxyhexenal (HHE) impairs glutamate transport in astrocyte cultures”, J. Alzheimer’s Dis. Epub ahead of print (2012).
- F.A. Schmitt, P.T. Nelson, E. Abner, S. Shceff, G.A. Jicha, C. Smith, G. Cooper, M. Mendiondo, D. D. Danner, L.J. Van Eldik, A. Caban-Holt, M.A. Lovell, and R.J. Kryscio, “University of Kentucky Sanders-Brown Healthy Brain Aging Volunteers: Donor charachteristics, procedures and neuropathology”, Curr. Alzheimer’s Res. 9:724-733, (2012).
- G. Lyubartseva and M.A. Lovell*, “A potential role for zinc alterations in the pathogenesis of Alzheimer’s disease” Invited Review, Biofactors, 38:98-106, (2012).
- A.M. Weidner, M.A. Bradley, T.L. Beckett, D.M. Niedowicz, A.L. Dowling, S.V. Matveev, H. Levine III, M.A. Lovell* and M.P. Murphy*, “RNA oxidation adducts 8-OHG change with Aß42 levels in late-stage Alzheimer’s disease”, PLoS One, 6:e24930, (2011).
- M.D. Timmons, M.A. Bradley, M.A. Lovell and B.C. Lynn, “Procedure for the isolation of mitochondria, cytosolic and nuclear material from a single piece of neurological tissue for high-throughput mass spectral analysis”, J. Neurosci. Methods 197:279-282, (2011).
- M.A. Lovell,* S. Soman and M.A. Bradley, “Increased DNA and RNA oxidation in Preclinical Alzheimer’s disease (PCAD) brain”, Mech. Aging and Dev., Invited article, Mech. Ageing Dev. 132:443-448, (2011).
- M.A. Bradley, S. Xiong, W. R. Markesbery and M.A. Lovell*, “Elevated 4-hydroxyhexenal in Alzheimer’s Disease (AD) Progression”, Neurobiol. Aging, [Epub ahead of print], (2010).
- M.A. Bradley, S. Xiong, W.R. Markesbery and M.A. Lovell*, “Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer’s disease (PCAD)”, Free Radic. Biol. Med., 48:1570-1576, (2010).
- B.C. Lynn, J. Wang, W.R. Markesbery and M.A. Lovell, “Quantitative Changes in the Mitochondrial Proteome from Subjects with Mild Cognitive Impairment, Early Stage, and Late-Stage Alzheimer’s Disease”, J. Alzheimer’s Dis. 19:325-339, (2010).
- G. Lyubartseva, J.L. Smith, W.R. Markesbery and M.A. Lovell*, “Alterations of Zinc Transporter Proteins ZnT-1, ZnT-4 and ZnT-6 in Preclinical Alzheimer’s Disease Brain”, Brain Pathol., 20:343-350, (2010).
- M.A. Lovell*, S. Xiong, G. Lyubartseva and W.R. Markesbery, “Organoselenium (Sel-Plex Diet) Decreases Amyloid Burden and RNA and DNA Oxidative Damage in APP/PS1 Mice”, Free Radic. Biol. Med., 46:1527-1533, (2009).
- Y.J. Fu, M.A. Lovell and B.C. Lynn, “Quantitative Proteomic Analysis of Mitochondria in Aging PS-1 Transgenic Mice”, Cell. Mol. Neurobiol., 29:649-664, (2009).
- M.A. Lovell*, “A Potential Role for Alterations of Zinc and Zinc Transport Proteins in the Progression of Alzheimer’s Disease”, (Invited Review) J. Alzheimer’s Disease, 16:471-483, (2009).
- C.D. Smith, H. Chebrolu, A.H. Andersen, D.A. Powell, M.A. Lovell, S. Xiong, and B.T. Gold, “White Matter Diffusion Alterations in Normal Women at Risk of Alzheimer’s Disease”, Neurobiol. Aging, 31:122-131 (2010) [Epub ahead of print; doi:10.1016/jneurobiolaging.2008.08.006], (2008).
- C. X. Shao, J. Wang, W. R. Markesbery and M. A. Lovell*, “Decreased Ogg1 Based Excision Repair in Amnestic Mild Cognitive Impairment”, Free Radic. Biol. Med. 45:813-819, (2008).
- J.A. Sonnen, J.C. Breitner, M.A. Lovell, W.R. Markesbery, J.F. Quinn and T.J. Montine, “Free Radical-Mediated Damage to Brain in Alzheimer’s Disease and its Transgenic Mouse Models”, (Invited Review) Free Radic. Biol. Med.45:219-230, (2008).
- M. A. Lovell*, B. C. Lynn, S. Xiong, J. F. Quinn, J. Kaye and W. R. Markesbery, “An Aberrant Protein Complex as a Biomarker of Alzheimer’s Disease”, Neurology, 70:2212-2218, (2008).
- M. A. Lovell* and W. R. Markesbery, “Oxidative Modification of RNA in Mild Cognitive Impairment”, Neurobiol. Dis., 29:169-175, (2008).
- M. A. Lovell* and W. R. Markesbery, “Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease”, (Invited Review) Nucleic Acids Res., 35:7497-9504, (2007).
- M.A. Lovell*, “Zinc transporters in the Progression of Alzheimer’s Disease”, In: Membrane Transporters in Drug Discovery and Development: Methods and Protocols, (Methods in Molecular Biology Series), Q. Yan, Ed., 2010.
- J. D. Robertson and M. A. Lovell, "Applications of Radioanalytical Chemistry to Alzheimer's Disease," In: Radioanalytical Methods in Interdisciplinary Research, C. A. Laue and K. L. Nash, Eds., 2004, pp. 298-306.
- M. A. Lovell and W. R. Markesbery, "Analysis of Aldehydic Markers of Lipid Peroxidation in Biological Tissues by High-Pressure Liquid Chromatography with Fluorescence Detection," In: Methods in Biological Oxidative Stress, K. Hensley, Ed., 2003, pp. 17-21.
- W. R. Markesbery, T. J. Montine and M. A. Lovell, "Oxidative Alteration in Neurodegenerative Diseases," In: The Pathogenesis of Neurodegenerative Disorders, M. P. Mattson, Ed., Humana Press, 2001, pp. 21-51.
- M. A. Lovell, W. D. Ehmann, W. R. Markesbery, S. Melethil, C. R. Swyt and P. F. Zatta, "Standardization in Biological Analyses of Aluminum: What are the Needs?" In: Research Issues in Aluminum Toxicity, R. A. Yokel and M. S. Golub, Eds., Taylor and Francis, 1997.