Dr. George Perry
Professor and Dean of College of Sciences
Our studies are focused on the mechanism of formation and physiological consequences of the cytopathology of Alzheimer disease. We have shown that oxidative damage is the initial cytopathology in Alzheimer disease. We are working to determine the sequence of events leading to neuronal oxidative damage and the source of the increased oxygen radicals. Our current studies focus on (i) the mechanism for RNA-based redox metal binding; (ii) the consequences of RNA oxidation on protein synthesis rate and fidelity; (iii) the role of redox active metals in mediating prooxidant and antioxidant properties; (iv) the signal transduction pathways altered in Alzheimer disease that allow neurons to evade apoptosis; and (v) mechanism of phosphorylation control of oxidative damage to neurofilament proteins
Castellani RJ, Nugent SL, Morrison AL, Zhu X, Lee H-g, Harris PLR, Bajić V, Sharma HS, Chen SG, Oettgen P, Perry G, Smith MA. CD3 in Lewy pathology: does the abnormal recall of neurodevelopmental processes underlie Parkinson’s disease. J Neural Transm 118:23-26, 2011.
Colom LV, Castaneda MT, Hernandez S, Perry G, Jaime S, Touham A. Intrahippocampal amyloid-β (1-40) injections injure medial septal neurons. Curr Alzheimer Res 8:832-840, 2011.
Castellani RJ, Gupta Y, Sheng B, Siedlak SL, Harris PLR, Coller JM, Perry G, Lee H-g, Tabaton M, Smith MA, Wang X, Zhu X. A novel origin for granulovacuolar degeneration in aging and Alzheimer’s disease: parallels to stress granules. Lab Invest 91:1777-1786, 2011.
Stone JG, Siedlak SL, Tabaton M, , Hirano A, Castellani RJ, Santocanale C, Perry G, Smith MA, Zhu X, Lee H-g. The cell cycle regulator, phosphorylated retinoblastoma protein, is associated with tau pathology in several tauopathies. J Neuropathol Exp Neurol 70:578-587, 2011.
Zhu X, Castellani RJ, Moreira PI, Aliev G, Shenk JC, Siedlak SL, Harris PLR, Fujioka H, Sayre LM, Szweda PA, Szweda LI, Smith MA, Perry G. Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover. Free Rad Biol Med 52:699-704, 2012.
Nunomura A, Tamaoki T, Motohashi N, Nakamura M, McKeel Jr. DW, Tabaton M, Lee H-g, Smith MA, Perry G, Zhu X. The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. J Neuropathol Exp Neurol 71:233-241, 2012.
Calderón-Garcidueñas L, Kavanaugh M, Block M, D’Angiulli A, Delgado-Chάvez R, Torres-Jardón R, González-Maciel A, Reynoso-Robles R, Perry G, Osnaya N, Villarreal-Calderon R, Guo R, Hua Z, Zhu H, Perry G, Diaz P. Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults. J Alzheimer’s Dis 28:93-107, 2012.
Valdez CM, Phelix CF, Smith MA, Perry G, Santamaria F. Modeling cholesterol metabolism by gene expression profiling in the hippocampus. Molecular Biosystems 7:1891-1901, 2011.
Gugliemotto M, Aragno M, Tamagno E, Vercellinatto I, Visentin S, Medana C, Catalano MG, Smith MA, Perry G, Danni O, Boccuzzi G, Tabaton M. AGEs/RAGE complex upregulates BACE1 via NF-κB pathway activation Neurobiol Aging 33:196e.13-196e.27, 2012.
Wang X, Su B, Liu W, He X, Gao Y, Castellani RJ, Perry G, Smith MA, Zhu X. DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinum toxicity in neurons: implications for Parkinson’s disease. Aging Cell 10:807-823, 2011.
Wise-Scira O, Xu L, Kitahara T, Perry G, Coskuner O. Amyloid-β peptide structure in aqueous solution varies with fragment size. J Chem Phys 135:205101-1–205101-13, 2011 (Virtual J Biol Phys Res, 22(11), 2011).
Paley EL, Sokolova O, Perry G. Tryptamine-induced Tryptophanyl-tRNA synthetase deficiency in axonopathy and mitochondriopathy mimicking neurodegenerative diseases Curr Alzheimer Res (accepted pending revision).
Sheng B, Wang X, Su B, Lee H-G, Casadesus G, Perry G, Zhu X. Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120:419-429, 2012.
Phelix CF, LeBaron RG, Roberson DJ, Villanueva RE, Villareal G, Rahimi OB, Siedlak S, Zhu X, Perry G. Transcription-to-metabalome biosimulation reveals human hippocampal hypometabolism with age and Alzheimer’s disease. Intern J Knowledge Discovery Bioinformatics 2:1-18, 2011.
Kudo W, Lee H-P, Zou W-Q, Perry G, Zhu X, Smith MA, Petersen RB, Lee H-G. Cellular prion protein is essential for oligomeric amyloid-β-induced neuronal cell death. Human Mol Genetics 21:1138-1144, 2012.
Wang X, Yan MH,Fujioka H, Liu J, Wilson-Delfosse A, Chen SG, Perry G, Casadesus G, Zhu X. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Human Mol Genetics 21:1931-1944, 2012.