Mark A Smith

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. pmc Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 94:9866-8. 1997
  2. ncbi request reprint Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 33:1194-9. 2002
  3. ncbi request reprint JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurochem 85:87-93. 2003
  4. ncbi request reprint Causes and consequences of oxidative stress in Alzheimer's disease
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 32:1049. 2002
  5. ncbi request reprint Amyloid-beta, tau alterations and mitochondrial dysfunction in Alzheimer disease: the chickens or the eggs?
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurochem Int 40:527-31. 2002
  6. ncbi request reprint Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Antioxid Redox Signal 2:413-20. 2000
  7. ncbi request reprint Oxidative stress in Alzheimer's disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1502:139-44. 2000
  8. ncbi request reprint Dimethylargininase, a nitric oxide regulatory protein, in Alzheimer disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 25:898-902. 1998
  9. ncbi request reprint Abnormal localization of iron regulatory protein in Alzheimer's disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Brain Res 788:232-6. 1998
  10. pmc The effect of mGluR2 activation on signal transduction pathways and neuronal cell survival
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Brain Res 1249:244-50. 2009

Collaborators

Detail Information

Publications108 found, 100 shown here

  1. pmc Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 94:9866-8. 1997
    ..Taken together, these findings indicate that iron accumulation could be an important contributor toward the oxidative damage of Alzheimer disease...
  2. ncbi request reprint Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 33:1194-9. 2002
    ..The notion that amyloid-beta and tau function as protective components brings into serious question the rationale of current therapeutic efforts targeted toward lesion removal...
  3. ncbi request reprint JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurochem 85:87-93. 2003
    ..Together, these findings lend further credence to the notion that the JNK/SAPK pathway is dysregulated in AD and also indicate an active role for this pathway in disease pathogenesis...
  4. ncbi request reprint Causes and consequences of oxidative stress in Alzheimer's disease
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 32:1049. 2002
  5. ncbi request reprint Amyloid-beta, tau alterations and mitochondrial dysfunction in Alzheimer disease: the chickens or the eggs?
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurochem Int 40:527-31. 2002
    ..However, this rationale may be misguided since new evidence from our laboratories and others suggest that the lesions not only occur as a by-product of the fundamental disease process but also that they may be protective...
  6. ncbi request reprint Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Antioxid Redox Signal 2:413-20. 2000
    ..Supporting this, we have considerable in vivo and in vitro evidence for mitotic disturbances in AD and its relationship with the pathogenesis of AD...
  7. ncbi request reprint Oxidative stress in Alzheimer's disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1502:139-44. 2000
    ....
  8. ncbi request reprint Dimethylargininase, a nitric oxide regulatory protein, in Alzheimer disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 25:898-902. 1998
    ..Finally, our results provide additional evidence that oxidative stress- and nitric oxide-mediated events play important roles in the pathogenesis of AD...
  9. ncbi request reprint Abnormal localization of iron regulatory protein in Alzheimer's disease
    M A Smith
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Brain Res 788:232-6. 1998
    ..Since IRP-2 colocalizes with redox-active iron, our results suggest that alterations in IRP-2 might be directly linked to impaired iron homeostasis in Alzheimer's disease...
  10. pmc The effect of mGluR2 activation on signal transduction pathways and neuronal cell survival
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Brain Res 1249:244-50. 2009
    ..Additionally, our findings lend support to the notion that tau phosphorylation is a neuroprotective antioxidant response to cellular insults...
  11. ncbi request reprint Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice
    Gjumrakch Aliev
    Microscopy Research Center, Department of Anatomy, Department of Pathology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA
    Neurol Res 25:665-74. 2003
    ..Our observations first time demonstrate that vascular wall cells, especially their mitochondria, appear to be a central target for oxidative stress induced damage...
  12. pmc Impaired balance of mitochondrial fission and fusion in Alzheimer's disease
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurosci 29:9090-103. 2009
    ..Based on these findings, we suggest that an altered balance in mitochondrial fission and fusion is likely an important mechanism leading to mitochondrial and neuronal dysfunction in AD brain...
  13. ncbi request reprint Increased p27, an essential component of cell cycle control, in Alzheimer's disease
    Osamu Ogawa
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Aging Cell 2:105-10. 2003
    ..The findings presented here suggest that dysregulation of the cell cycle plays a crucial role in the pathogenesis of Alzheimer's disease that may provide a novel mechanistic basis for therapeutic intervention...
  14. ncbi request reprint Ribosomal RNA in Alzheimer disease is oxidized by bound redox-active iron
    Kazuhiro Honda
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 280:20978-86. 2005
    ....
  15. ncbi request reprint Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA
    Antioxid Redox Signal 5:571-6. 2003
    ....
  16. pmc Down-regulation of serum gonadotropins is as effective as estrogen replacement at improving menopause-associated cognitive deficits
    Kathryn J Bryan
    Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio, USA
    J Neurochem 112:870-81. 2010
    ..These findings provide a potential novel protective strategy to treat menopause/age-related cognitive decline and/or prevent the development of AD...
  17. ncbi request reprint Autophagocytosis of mitochondria is prominent in Alzheimer disease
    Paula I Moreira
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    J Neuropathol Exp Neurol 66:525-32. 2007
    ..Whether increased autophagocytosis is a consequence of an increased turnover of mitochondria or whether the mitochondria in Alzheimer disease are more susceptible to autophagy remains to be resolved...
  18. pmc DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson's disease
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, 2103 Connell Road, Cleveland, OH 44106, USA
    Aging Cell 10:807-23. 2011
    ..Overall, these findings suggest that DLP1-dependent mitochondrial fragmentation plays a crucial role in mediating MPP(+) -induced mitochondria abnormalities and cellular dysfunction and may represent a novel therapeutic target for PD...
  19. pmc Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Free Radic Biol Med 52:699-704. 2012
    ..These findings directly implicate lipid crosslinking peroxidation products as accumulating not in the lesions or the lipofuscin pathways, but instead in a distinct pathway, GVD, that accumulates cytosolic proteins...
  20. ncbi request reprint Metal ions and oxidative protein modification in neurological disease
    Lawrence M Sayre
    Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
    Ann Ist Super Sanita 41:143-64. 2005
    ....
  21. pmc Vascular oxidative stress in Alzheimer disease
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurol Sci 257:240-6. 2007
    ..Here, we discuss vascular factors in relation to Alzheimer disease and review hypoperfusion as a potential cause by triggering mitochondrial dysfunction and increased oxidative stress initiating the pathogenic process...
  22. pmc Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease
    Sandra L Siedlak
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Free Radic Res 43:156-64. 2009
    ....
  23. ncbi request reprint Tau modifiers as therapeutic targets for Alzheimer's disease
    Quan Liu
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA
    Biochim Biophys Acta 1739:211-5. 2005
    ..Biochemical findings show that tau oxidative modifications are regulated by phosphorylation and that tau found in neurofibrillary tangles is oxidatively modified, suggesting that tau is closely linked to the biology, not toxicity, of AD...
  24. pmc Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Drugs Aging 27:181-92. 2010
    ..e. mitochondrial protection) that has the potential to significantly deter AD progression if adequately developed. Current treatment strategies under investigation are described in this review...
  25. ncbi request reprint Neuroprotective properties of Bcl-w in Alzheimer disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    J Neurochem 89:1233-40. 2004
    ..Taken together, these series of results suggest that Bcl-w may play an important protective role in neurons in the diseased brain and that this aspect could be therapeutically harnessed to afford neuroprotection...
  26. ncbi request reprint Compensatory responses induced by oxidative stress in Alzheimer disease
    Paula I Moreira
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44100, USA
    Biol Res 39:7-13. 2006
    ..These findings suggest that Alzheimer disease is associated with a novel balance in oxidant homeostasis...
  27. pmc The cell cycle regulator phosphorylated retinoblastoma protein is associated with tau pathology in several tauopathies
    Jeremy G Stone
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    J Neuropathol Exp Neurol 70:578-87. 2011
    ..These observations further implicate aberrant neuronal cell cycle progression in neurodegenerative diseases, particularly tauopathies, and suggest a novel target for therapeutic intervention...
  28. ncbi request reprint Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease
    Rudy J Castellani
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Ageing Res Rev 3:319-26. 2004
    ....
  29. ncbi request reprint Increased expression of p130 in Alzheimer disease
    Laura A Previll
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Neurochem Res 32:639-44. 2007
    ..Our data suggest that, despite its upregulation, the aberrant localization of p130 to the neuronal cytoplasm facilitates neuronal cell cycle re-entry in AD...
  30. pmc The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, 2103 Cornell Rd, Cleveland, OH 44106, USA
    Am J Pathol 174:891-7. 2009
    ....
  31. ncbi request reprint Signal transduction cascades associated with oxidative stress in Alzheimer's disease
    Robert B Petersen
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Alzheimers Dis 11:143-52. 2007
    ..In this review, we present the evidence of oxidative stress and compensatory responses that occur in Alzheimer's disease with a particular focus on the roles and mechanism of activation of stress-activated protein kinase pathways...
  32. ncbi request reprint Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients
    Hossein A Ghanbari
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Aging Cell 3:41-4. 2004
    ..Primary culture of human olfactory neurons will be useful in understanding the mechanism of oxidative damage in Alzheimer's disease and can even be utilized in developing therapeutic strategies...
  33. ncbi request reprint The cell cycle in Alzheimer disease: a unique target for neuropharmacology
    Kate M Webber
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Mech Ageing Dev 126:1019-25. 2005
    ..Therefore, therapeutic interventions targeted toward ameliorating mitotic changes would be predicted to have a profound and positive impact on Alzheimer disease progression...
  34. ncbi request reprint Oxidative stress: the old enemy in Alzheimer's disease pathophysiology
    Paula I Moreira
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Curr Alzheimer Res 2:403-8. 2005
    ....
  35. doi request reprint Chronic oxidative stress causes increased tau phosphorylation in M17 neuroblastoma cells
    Bo Su
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Neurosci Lett 468:267-71. 2010
    ..In conclusion we suggest that chronic oxidative stress contributes to increased tau phosphorylation in vitro and could play a critical role in neurofibrillary pathology in vivo...
  36. pmc Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
    Neurochem Int 54:84-8. 2009
    ..Therefore, the study of aberrant cell cycle regulation in model systems, both cellular and animal, may provide extremely important insights into the pathogenesis of AD and also serve as a means to test novel therapeutic approaches...
  37. ncbi request reprint Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations
    Quan Liu
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Free Radic Biol Med 38:746-54. 2005
    ....
  38. ncbi request reprint Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA
    J Alzheimers Dis 9:147-53. 2006
    ....
  39. ncbi request reprint Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases?
    George Perry
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 33:1475-9. 2002
    ..Although much data remain to be collected, the broad spectrum of changes found in AD are only seen, albeit to a lesser extent, in normal aging with other neurodegenerative diseases showing distinct spectrums of change...
  40. ncbi request reprint Tau phosphorylation in Alzheimer's disease: pathogen or protector?
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106 USA
    Trends Mol Med 11:164-9. 2005
    ....
  41. doi request reprint Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease
    Jaewon Chang
    Department of Neuroscience, Case Western Reserve University, Cleveland, OH 44106, USA
    Neurobiol Aging 33:2062-71. 2012
    ....
  42. ncbi request reprint Therapeutic opportunities in Alzheimer disease: one for all or all for one?
    Michael W Marlatt
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA
    Curr Med Chem 12:1137-47. 2005
    ..In this review, the scientific basis for common AD therapeutics as well as the efficacy of these treatments will be discussed...
  43. ncbi request reprint Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe?
    Osamu Ogawa
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Acta Neuropathol 105:524-8. 2003
    ..Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD...
  44. ncbi request reprint Estrogen bows to a new master: the role of gonadotropins in Alzheimer pathogenesis
    Kate M Webber
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Rd, Cleveland, OH 44106, USA
    Ann N Y Acad Sci 1052:201-9. 2005
    ..On this basis, we suggest that the results of the WHI Memory Study are not only predictable but also avoidable by therapeutically targeting the gonadotropins instead of the sex steroids...
  45. ncbi request reprint Redox metals and oxidative abnormalities in human prion diseases
    Robert B Petersen
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Acta Neuropathol 110:232-8. 2005
    ..These findings suggest an important distinction in prion-related oxidative stress, indicating that different neurodegenerative pathways are involved in different prion diseases...
  46. ncbi request reprint Increased autophagic degradation of mitochondria in Alzheimer disease
    Paula I Moreira
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Autophagy 3:614-5. 2007
    ..The study of autophagy in Alzheimer disease could clarify the mechanisms underlying this neurodegenerative disorder and, eventually, help in the development of new therapeutic strategies...
  47. pmc Biomarkers in Alzheimer's disease: past, present and future
    Katarzyna Gustaw-Rothenberg
    University Hospitals, Case Medical Center and University Memory and Cognitive Center, Case Western Reserve University, Cleveland, OH, USA
    Biomark Med 4:15-26. 2010
    ....
  48. ncbi request reprint Indices of metabolic dysfunction and oxidative stress
    Gemma Casadesus
    Department of Neuroscience, Case Western Reserve University, Cleveland, OH, USA
    Neurochem Res 32:717-22. 2007
    ..Overall, clarifying cellular and molecular manifestations involved in metabolic alterations may contribute to a better understanding of early Alzheimer disease pathophysiology...
  49. ncbi request reprint A second look into the oxidant mechanisms in Alzheimer's disease
    Paula I Moreira
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA
    Curr Neurovasc Res 2:179-84. 2005
    ....
  50. ncbi request reprint Aberrant expression of metabotropic glutamate receptor 2 in the vulnerable neurons of Alzheimer's disease
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Acta Neuropathol 107:365-71. 2004
    ..Immunocytochemical examination revealed considerable overlap between mGluR2 and neurofibrillary alterations. Thus, it is likely that mGluR2 represents a novel therapeutic target for AD...
  51. ncbi request reprint Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease
    George Perry
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA
    Biometals 16:77-81. 2003
    ....
  52. pmc Antimicrobial peptide β-defensin-1 expression is upregulated in Alzheimer's brain
    Wesley M Williams
    Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, 2124 Cornell Rd, Cleveland, OH 44106, USA
    J Neuroinflammation 10:127. 2013
    ..We assessed the expression of hBD-1, -2, and -3 in tissue obtained at autopsy from AD and age-matched control brains...
  53. ncbi request reprint Therapeutic options in Alzheimer's disease
    Paula I Moreira
    Case Western Reserve University, Department of Pathology, Cleveland, Ohio 44106, USA
    Expert Rev Neurother 6:897-910. 2006
    ..The possibility that oxidative stress is a primary event in AD indicates that antioxidant-based therapies are perhaps the most promising weapons against this devastating neurodegenerative disorder...
  54. ncbi request reprint Ectopic expression of phospho-Smad2 in Alzheimer's disease: uncoupling of the transforming growth factor-beta pathway?
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurosci Res 84:1856-61. 2006
    ....
  55. pmc Cellular prion protein is essential for oligomeric amyloid-β-induced neuronal cell death
    Wataru Kudo
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Hum Mol Genet 21:1138-44. 2012
    ..These findings are the first to demonstrate that PrP(C) is required for Aβ oligomer-induced neuronal cell death, the pathology essential to cognitive loss...
  56. ncbi request reprint Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurosci Res 75:698-703. 2004
    ..Therefore, therapeutics targeted toward initiators of the cell cycle are likely to prove of great efficacy for the treatment of AD...
  57. ncbi request reprint The role of iron and copper in the aetiology of neurodegenerative disorders: therapeutic implications
    George Perry
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    CNS Drugs 16:339-52. 2002
    ..In this article, we examine not only the possible mechanism of disease but also how pharmaceuticals may intervene, from direct and indirect antioxidant therapy to strategies involving gene therapy...
  58. doi request reprint Oxidative stress in Alzheimer disease: a possibility for prevention
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Neuropharmacology 59:290-4. 2010
    ..In this review, we elaborate on the dynamic role of oxidative stress in AD and present corresponding treatment strategies that are currently under investigation...
  59. ncbi request reprint Distribution, levels, and activation of MEK1 in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurochem 86:136-42. 2003
    ..Together, these findings lend further credence to the notion that the ERK pathway is dysregulated in AD and also indicate an active role for this pathway in disease pathogenesis...
  60. pmc Microtubule reduction in Alzheimer's disease and aging is independent of tau filament formation
    Adam D Cash
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Am J Pathol 162:1623-7. 2003
    ..016). These findings suggest that reduction in microtubule assembly is not dependent on tau abnormalities of AD and aging...
  61. ncbi request reprint The state versus amyloid-beta: the trial of the most wanted criminal in Alzheimer disease
    Catherine A Rottkamp
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Peptides 23:1333-41. 2002
    ..Below, we present a brief synopsis of the trial for you, the jury, to decide the verdict. Amyloid-beta: guilty or not-guilty?..
  62. ncbi request reprint Iron homeostasis is maintained in the brain, but not the liver, following mild hypoxia
    Glenda M Bishop
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Redox Rep 12:257-66. 2007
    ..Together, these results indicate that there is a tighter regulation of iron metabolism in the brain than the liver, which limits the redistribution of Fe3+ following hypoxia...
  63. pmc Novel therapeutics for Alzheimer's disease: an update
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Curr Opin Drug Discov Devel 13:235-46. 2010
    ..Current hypotheses for the pathogenesis of AD are discussed in this review, with a particular emphasis on the implications of these hypotheses with respect to treatment strategies and preventive measures...
  64. ncbi request reprint Role of mitochondrial dysfunction in Alzheimer's disease
    Rudy Castellani
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurosci Res 70:357-60. 2002
    ..Here we review the causes and consequences of mitochondrial disturbances in Alzheimer's disease as well as how this information might impact on therapeutic approaches to this disease...
  65. ncbi request reprint Amyloid-beta: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-beta
    Craig S Atwood
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Brain Res Brain Res Rev 43:1-16. 2003
    ..ccirf;), leading to enhanced, rather than reduced, neuronal oxidative stress...
  66. ncbi request reprint Is nitric oxide a key target in the pathogenesis of brain lesions during the development of Alzheimer's disease?
    Ali Aliyev
    Microscopy Research Center, Case Western Reserve University, Cleveland, OH 44106, USA
    Neurol Res 26:547-53. 2004
    ..We speculate that pharmacological intervention using NO donors and/or NO suppressors will be able to delay or minimize the development of brain pathology and further progression of mental retardation...
  67. ncbi request reprint Mitochondria DNA deletions in atherosclerotic hypoperfused brain microvessels as a primary target for the development of Alzheimer's disease
    Ali Aliyev
    The Microscopy Research Center, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurol Sci 229:285-92. 2005
    ..Therefore, selective pharmacological intervention, directed for abolishing the chronic hypoperfusion state, would possibly change the natural course of development of dementing neurodegeneration...
  68. ncbi request reprint Alzheimer disease: evidence for a central pathogenic role of iron-mediated reactive oxygen species
    Gemma Casadesus
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Alzheimers Dis 6:165-9. 2004
    ..In this review, we consider the wealth of evidence implicating a central role for metals in Alzheimer disease...
  69. ncbi request reprint Mitogen- and stress-activated protein kinase 1: convergence of the ERK and p38 pathways in Alzheimer's disease
    Kate M Webber
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurosci Res 79:554-60. 2005
    ....
  70. ncbi request reprint Mitochondrial failures in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Am J Alzheimers Dis Other Demen 19:345-52. 2004
    ..Future studies comparing the spectrum of mitochondrial damage and the relationship to oxidative stress-induced damage during the aging process or, more importantly, during the maturation of AD pathology are warranted...
  71. ncbi request reprint High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal
    Takafumi Wataya
    Institute of Pathology and Departments of Physiology and Biophysics, and Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 277:4644-8. 2002
    ....
  72. ncbi request reprint Amyloid-beta: a (life) preserver for the brain
    Mark E Obrenovich
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurobiol Aging 23:1097-9. 2002
  73. ncbi request reprint Oxidative stress and neurotoxicity
    Lawrence M Sayre
    Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Chem Res Toxicol 21:172-88. 2008
    ..Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field...
  74. ncbi request reprint c-Jun phosphorylation in Alzheimer disease
    Akanksha Thakur
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurosci Res 85:1668-73. 2007
    ..Overall, this study demonstrated specific alterations in c-Jun phosphorylation and distribution in AD which is not necessarily linked to apoptosis but rather may represent an adaptation process in the face of oxidative stress...
  75. ncbi request reprint Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence
    Jian Dong
    Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Biochemistry 42:2768-73. 2003
    ..The results also reveal a direct chemical basis for oxidative damage caused by amyloid-beta protein in AD...
  76. ncbi request reprint Is Alzheimer's disease a mitochondrial disorder?
    Adam D Cash
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Neuroscientist 8:489-96. 2002
    ..Supporting this, the authors have considerable in vivo and in vitro evidence for mitotic disturbances in AD...
  77. ncbi request reprint Challenging the amyloid cascade hypothesis: senile plaques and amyloid-beta as protective adaptations to Alzheimer disease
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Ann N Y Acad Sci 1019:1-4. 2004
    ..With this in mind, we suspect that current therapeutic efforts targeted toward lowering amyloid-beta production or removal of deposited amyloid-beta will only serve to exacerbate the disease process...
  78. ncbi request reprint The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau
    Anthony W Hartzler
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurobiol Aging 23:855-9. 2002
    ..Based on these findings, we propose that the phosphorylation of tau is a direct consequence of the oxidative stress-induced activation of mitogen-activated protein kinases, including p38...
  79. ncbi request reprint Is intraneuronal amyloid beta-peptide accumulation the trigger of Alzheimer's disease pathophysiology?
    Paula I Moreira
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Alzheimers Dis 6:433-4; discussion 443-9. 2004
  80. ncbi request reprint Presenilin mutation: a deadly first hit in Alzheimer disease. A commentary on "aging sensitizes towards ROS formation and lipid peroxidation in PS1M146L transgenic mice"
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, OH 44106, USA
    Free Radic Biol Med 40:737-9. 2006
  81. ncbi request reprint Amyloid-beta: a vascular sealant that protects against hemorrhage?
    Craig S Atwood
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106 USA
    J Neurosci Res 70:356. 2002
  82. ncbi request reprint Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins
    Craig S Atwood
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Peptides 23:1343-50. 2002
    ....
  83. ncbi request reprint Hydroxynonenal adducts indicate a role for lipid peroxidation in neocortical and brainstem Lewy bodies in humans
    Rudy J Castellani
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurosci Lett 319:25-8. 2002
    ..These findings not only support prior studies indicating that lipid peroxidation is increased in patients with PD and DLBD but that oxidative damage may play a critical role in Lewy body formation...
  84. ncbi request reprint Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: beyond damage and response
    George Perry
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA
    Comp Biochem Physiol C Toxicol Pharmacol 133:507-13. 2002
    ..Thus, Alzheimer disease could be seen as part of normal aging that includes additional pathology due to inadequate homeostatic response...
  85. ncbi request reprint Insights into amyloid-beta-induced mitochondrial dysfunction in Alzheimer disease
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Free Radic Biol Med 43:1569-73. 2007
    ..Here, we review the role that amyloid-beta plays in mitochondrial structure and function of neurons and the importance of this in the pathogenesis of Alzheimer disease...
  86. ncbi request reprint Amyotrophic lateral sclerosis: a novel hypothesis involving a gained 'loss of function' in the JNK/SAPK pathway
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Redox Rep 8:129-33. 2003
    ..The involvement of the JNK/SAPK pathway integrates our knowledge about these two known genetic factors into a single pathogenic pathway involved in both sporadic and familial ALS...
  87. pmc Treating the lesions, not the disease
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, 2103 Cornell Rd, Cleveland, OH 44106, USA
    Am J Pathol 170:1457-9. 2007
  88. ncbi request reprint Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Azheimer disease
    Gjumrakch Aliev
    The Microscopy Research Center and Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland OH 44106, USA
    Neurotox Res 5:491-504. 2003
    ....
  89. ncbi request reprint A metabolic basis for Alzheimer disease
    George Perry
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Neurochem Res 28:1549-52. 2003
    ..Here we present data indicating that metabolic rate, nutrition, and neuronal size are all early indicators of AD. Understanding the cellular and molecular basis for these changes may open a new dimension to understanding AD...
  90. ncbi request reprint Tipping the apoptotic balance in Alzheimer's disease: the abortosis concept
    Arun K Raina
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Cell Biochem Biophys 39:249-55. 2003
    ..This review discusses the concept of abortosis in relation to Alzheimer's disease...
  91. ncbi request reprint P38 activation mediates amyloid-beta cytotoxicity
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA
    Neurochem Res 30:791-6. 2005
    ..Taken together, these data suggest that p38 is a key downstream effector of amyloid-beta-induced neuronal death and blocking this pathway may be of therapeutic value...
  92. ncbi request reprint Copper mediates dityrosine cross-linking of Alzheimer's amyloid-beta
    Craig S Atwood
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 43:560-8. 2004
    ..Given the elevated concentration of Cu in senile plaques, our results suggest that Cu interactions with Abeta could be responsible for causing the covalent cross-linking of Abeta in these structures...
  93. ncbi request reprint Involvement of oxidative stress in Alzheimer disease
    Akihiko Nunomura
    Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa, Japan
    J Neuropathol Exp Neurol 65:631-41. 2006
    ....
  94. ncbi request reprint Clusterin up-regulation following sub-lethal oxidative stress and lipid peroxidation in human neuroblastoma cells
    Paola Strocchi
    Department of Pharmacology, University of Bologna, Bologna 40126, Italy
    Neurobiol Aging 27:1588-94. 2006
    ....
  95. ncbi request reprint Neuropathology in Alzheimer's disease: awaking from a hundred-year-old dream
    Akihiko Nunomura
    Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa 078 8510, Japan
    Sci Aging Knowledge Environ 2006:pe10. 2006
    ..Moreover, if this concept holds true for pathology in other neurodegenerative diseases, we may need to restructure our thinking and undergo a paradigm shift before substantial progress can be made in therapeutic intervention...
  96. ncbi request reprint Antioxidant protection and neurodegenerative disease: the role of amyloid-beta and tau
    Rudy J Castellani
    Department of Pathology, University of Maryland, Baltimore, Maryland, USA
    Am J Alzheimers Dis Other Demen 21:126-30. 2006
    ....
  97. ncbi request reprint Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease
    Etsuro Matsubara
    Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
    J Neurochem 85:1101-8. 2003
    ..These findings may bear relevance to the pathogenesis and therapy of AD...
  98. doi request reprint Nucleic acid oxidation in Alzheimer disease
    Paula I Moreira
    Center for Neuroscience and Cell Biology, Institute of Physiology Faculty of Medicine, University of Coimbra, Coimbra, Portugal
    Free Radic Biol Med 44:1493-505. 2008
    ..Furthermore, we outline the mechanisms of nucleic acid oxidation and repair. Finally, evidence showing the occurrence of nucleic acid oxidation in Alzheimer disease will be discussed...
  99. ncbi request reprint Iron: the Redox-active center of oxidative stress in Alzheimer disease
    Rudy J Castellani
    Department of Pathology, University of Maryland, Baltimore, MD, USA
    Neurochem Res 32:1640-5. 2007
    ..In this review, we discuss the role of iron in the progression of AD...
  100. ncbi request reprint Neuropathology and treatment of Alzheimer disease: did we lose the forest for the trees?
    Rudy J Castellani
    University of Maryland, Department of Pathology, Baltimore, MD 21201, USA
    Expert Rev Neurother 7:473-85. 2007
    ..An acceptance that lesion-based therapies do not address etiology or rate-limiting pathogenic factors is probably necessary for the best chance of significant advances that have thus far been elusive...