Xiongwei Zhu

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. 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
  2. doi request reprint Abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Alzheimers Dis 33:S253-62. 2013
  3. pmc Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurochem 121:830-9. 2012
  4. 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
  5. pmc Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease
    Kathryn J Bryan
    Department of Neurosciences, Case Western Reserve University, Cleveland Ohio, USA
    Mol Neurodegener 3:13. 2008
  6. ncbi request reprint Insulin signaling, diabetes mellitus and risk of Alzheimer disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Alzheimers Dis 7:81-4. 2005
  7. ncbi request reprint Oxidative imbalance in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA
    Mol Neurobiol 31:205-17. 2005
  8. 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
  9. ncbi request reprint Alzheimer disease, the two-hit hypothesis: an update
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1772:494-502. 2007
  10. ncbi request reprint MAPKs are differentially modulated in arctic ground squirrels during hibernation
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurosci Res 80:862-8. 2005

Collaborators

Detail Information

Publications104 found, 100 shown here

  1. 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...
  2. doi request reprint Abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Alzheimers Dis 33:S253-62. 2013
    ....
  3. pmc Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurochem 121:830-9. 2012
    ..Taken together, these studies suggest that DJ-1 is involved in the regulation of mitochondrial dynamics through modulation of DLP1 expression and PD-associated DJ-1 mutations may cause PD by impairing mitochondrial dynamics and function...
  4. 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...
  5. pmc Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease
    Kathryn J Bryan
    Department of Neurosciences, Case Western Reserve University, Cleveland Ohio, USA
    Mol Neurodegener 3:13. 2008
    ..This is the first finding to our knowledge that CD74 is increased in neurons of AD cases compared to age-matched control cases...
  6. ncbi request reprint Insulin signaling, diabetes mellitus and risk of Alzheimer disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Alzheimers Dis 7:81-4. 2005
  7. ncbi request reprint Oxidative imbalance in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA
    Mol Neurobiol 31:205-17. 2005
    ..In this review, we present the evidence for oxidative stress in Alzheimer's disease and its likely sources and consequence in relation to other pathological changes...
  8. 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...
  9. ncbi request reprint Alzheimer disease, the two-hit hypothesis: an update
    Xiongwei Zhu
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Biochim Biophys Acta 1772:494-502. 2007
    ....
  10. ncbi request reprint MAPKs are differentially modulated in arctic ground squirrels during hibernation
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Neurosci Res 80:862-8. 2005
    ..Taken together, the differential modulation of the MAPK pathways may be critical for neuroprotection of AGS necessary for fluctuations in oxygen and nutrient delivery during hibernation...
  11. 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...
  12. pmc Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease
    Bo Su
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Mol Neurodegener 4:32. 2009
    ..In light of the known interaction of FOXO3 and 14-3-3, basic protein-protein interaction between these proteins and alpha-synuclein may be key...
  13. pmc The mitochondrial dynamics of Alzheimer's disease and Parkinson's disease offer important opportunities for therapeutic intervention
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Curr Pharm Des 17:3374-80. 2011
    ..We here discuss the role of mitochondrial dynamics in AD and PD and assess the need for their therapeutic exploitation...
  14. pmc Role of metal dyshomeostasis in Alzheimer's disease
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Metallomics 3:267-70. 2011
    ..We here elaborate on the roles of iron, copper, and zinc in AD and describe the therapeutic implications they present...
  15. 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...
  16. 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...
  17. pmc Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 105:19318-23. 2008
    ....
  18. 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...
  19. pmc Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease
    Baiyang Sheng
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurochem 120:419-29. 2012
    ..Overall, this study demonstrated that impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD...
  20. 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...
  21. 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...
  22. 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
    ....
  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. 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...
  25. ncbi request reprint Distribution, levels and phosphorylation of Raf-1 in Alzheimer's disease
    Matthew Mei
    Department of Pathology, Case Western Reserve University, and MetroHealth Medical Center, Cleveland, Ohio 44106, USA
    J Neurochem 99:1377-88. 2006
    ..Based on these findings, we speculate that Raf-1 is activated to effectively mediate Ras-dependent signals in Alzheimer's disease...
  26. 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
    ....
  27. 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...
  28. pmc LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Hum Mol Genet 21:1931-44. 2012
    ..We concluded that LRRK2 regulates mitochondrial dynamics by increasing mitochondrial DLP1 through its direct interaction with DLP1, and LRRK2 kinase activity plays a critical role in this process...
  29. 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
    ....
  30. 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
    ....
  31. 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...
  32. pmc Reexamining Alzheimer's disease: evidence for a protective role for amyloid-beta protein precursor and amyloid-beta
    Rudy J Castellani
    Department of Pathology, University of Maryland, Baltimore, MD 21201, USA
    J Alzheimers Dis 18:447-52. 2009
    ..It is now long overdue that the neuroscientists avoid the pitfall of perseverating on "proteinopathies'' and recognize that the continued targeting of end stage lesions in the face of repeated failure, or worse, is a losing proposition...
  33. 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...
  34. 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...
  35. 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...
  36. 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
    ....
  37. 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
    ....
  38. 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
    ....
  39. 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
    ....
  40. 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...
  41. 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...
  42. 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
    ....
  43. 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...
  44. 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
    ....
  45. 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...
  46. pmc Widespread distribution of reticulon-3 in various neurodegenerative diseases
    Jonathon E Heath
    Department of Pathology, University of Maryland, Baltimore, Maryland, USA
    Neuropathology 30:574-9. 2010
    ....
  47. 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...
  48. 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...
  49. 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...
  50. 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
    ....
  51. 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...
  52. pmc Alzheimer disease pathology as a host response
    Rudy J Castellani
    Department of Pathology, University of Maryland, Baltimore, Maryland, USA
    J Neuropathol Exp Neurol 67:523-31. 2008
    ..Therefore, renewed efforts aimed at elucidating fundamental age-related processes such as oxidative stress and/or inflammatory mediators are warranted...
  53. 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...
  54. 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
    ....
  55. 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...
  56. 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...
  57. 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...
  58. pmc The essential role of ERK in 4-oxo-2-nonenal-mediated cytotoxicity in SH-SY5Y human neuroblastoma cells
    Hyun Pil Lee
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    J Neurochem 108:1434-41. 2009
    ..Overall, these data strongly suggest that ERK plays an essential role in ONE-mediated cytotoxicity and that ERK is an upstream component of p53-mediated apoptosis...
  59. 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...
  60. 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...
  61. 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...
  62. ncbi request reprint Aberrant localization of importin alpha1 in hippocampal neurons in Alzheimer disease
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Brain Res 1124:1-4. 2006
    ..These data suggest a hindrance in importin-mediated cytoplasmic-nuclear transport in AD...
  63. pmc Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease
    David J Bonda
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Redox Rep 15:161-8. 2010
    ....
  64. 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...
  65. ncbi request reprint Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    J Pharmacol Exp Ther 321:823-9. 2007
    ..To determine which hypothesis relates best to Alzheimer disease requires a broader view of disease pathogenesis and is discussed herein...
  66. 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...
  67. 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...
  68. 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...
  69. pmc Leucine-rich repeat kinase 2 colocalizes with alpha-synuclein in Parkinson's disease, but not tau-containing deposits in tauopathies
    George Perry
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
    Neurodegener Dis 5:222-4. 2008
    ..Mutations in leucine-rich repeat kinase 2 (LRRK2) are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease...
  70. pmc BRCA1 may modulate neuronal cell cycle re-entry in Alzheimer disease
    Teresa A Evans
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Int J Med Sci 4:140-5. 2007
    ....
  71. doi request reprint Antioxidant approaches for the treatment of Alzheimer's disease
    Hyun Pil Lee
    Case Western Reserve University, OH, USA
    Expert Rev Neurother 10:1201-8. 2010
    ..In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches...
  72. ncbi request reprint The role of mitogen-activated protein kinase pathways in Alzheimer's disease
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurosignals 11:270-81. 2002
    ..e., tau phosphorylation and amyloid-beta deposition, as well as the functional association to amyloid beta protein precursor. We suggest that regulation of these pathways may be a central facet to any potential treatment for the disease...
  73. 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...
  74. 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...
  75. 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...
  76. 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...
  77. pmc Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment
    Mark A Smith
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Alzheimers Dis 19:363-72. 2010
    ..Iron deposition at the preclinical stage of AD may be useful as a diagnostic tool, using iron imaging methods, as well as a potential therapeutic target, through metal ion chelators...
  78. pmc Abnormal mitochondrial dynamics--a novel therapeutic target for Alzheimer's disease?
    Bo Su
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Mol Neurobiol 41:87-96. 2010
    ..Based on this discussion, we propose that mitochondrial dynamics could be a potential therapeutic target for AD...
  79. ncbi request reprint Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats
    Gemma Casadesus
    USDA, HNRC on Aging at Tufts University, Boston, MA, USA
    Nutr Neurosci 7:309-16. 2004
    ..Therefore, cognitive improvements afforded by polyphenolic-rich fruits such as blueberries appear, in part, to be mediated by their effects on hippocampal plasticity...
  80. pmc Amyloid-beta42 interacts mainly with insoluble prion protein in the Alzheimer brain
    Wen Quan Zou
    Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 286:15095-105. 2011
    ..Although this work indicated the interaction of Aβ42 with huPrP in the AD brain, the pathophysiological relevance of the iPrP/Aβ42 interaction remains to be established...
  81. ncbi request reprint Chronological primacy of oxidative stress in Alzheimer disease
    Mark A Smith
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Neurobiol Aging 26:579-80. 2005
  82. 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...
  83. ncbi request reprint Perspectives on the amyloid-beta cascade hypothesis
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    J Alzheimers Dis 6:137-45. 2004
    ..These findings bring into serious doubt the validity of the Amyloid Cascade Hypothesis as the central cause of Alzheimer disease and, consequently, the potential usefulness of therapeutic targets against amyloid-beta...
  84. 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...
  85. pmc Cell cycle re-entry and mitochondrial defects in myc-mediated hypertrophic cardiomyopathy and heart failure
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America
    PLoS ONE 4:e7172. 2009
    ....
  86. pmc All-trans retinoic acid as a novel therapeutic strategy for Alzheimer's disease
    Hyun Pil Lee
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Expert Rev Neurother 9:1615-21. 2009
    ..Here, we review the actions of retinoic acid that indicate that it may have therapeutic properties ideally served for the treatment of neurodegenerative diseases such as Alzheimer's disease...
  87. ncbi request reprint The (un)balance between metabolic and oxidative abnormalities and cellular compensatory responses in Alzheimer disease
    Paula I Moreira
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Mech Ageing Dev 127:501-6. 2006
    ..However, in the initial stages of disease development, neurons adapt to the oxidative environment through the development of compensatory responses resulting in a shift of neuronal priority from normal function to basic survival...
  88. ncbi request reprint Prevention and treatment of Alzheimer disease and aging: antioxidants
    Quan Liu
    Department of Ophthalmology, University of California San Diego, 9500 Gilman Drive 0946, La Jolla, CA 92093 0946, USA
    Mini Rev Med Chem 7:171-80. 2007
    ..As such, therapeutic modalities encompassing antioxidants may be an effective approach to the treatment of neurodegenerative diseases and delay the aging process...
  89. 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...
  90. ncbi request reprint Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels
    Yi Long Ma
    Institute of Arctic Biology, Alaska Basic Neuroscience Program, Box 757000, 902 N Koyukuk Dr, Irving I Rm 311, University of Alaska Fairbanks, Fairbanks, AK 99775 7000, USA
    Am J Physiol Regul Integr Comp Physiol 289:R1297-306. 2005
    ..These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal...
  91. 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
    ....
  92. ncbi request reprint Ferric cycle activity and Alzheimer disease
    Barney E Dwyer
    Research Service, VA Medical and Regional Office Center, White River Junction, Vermont 05009, USA
    Curr Neurovasc Res 2:261-7. 2005
    ....
  93. ncbi request reprint Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts
    Paula I Moreira
    Center for Neuroscience and Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal
    J Alzheimers Dis 12:195-206. 2007
    ..These data suggest mitochondria are important in oxidative damage that occurs in AD. As such, antioxidant therapies based on lipoic acid and N-acetyl cysteine supplementation may be promising...
  94. pmc Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein
    Elena Tamagno
    Department of Experimental Medicine and Oncology, University of Torino, Torino, Italy
    J Neurochem 104:683-95. 2008
    ..Our findings suggest a mechanism by which OS induces BACE1 transcription, thereby promoting production of pathological levels of amyloid beta in AD...
  95. ncbi request reprint Alzheimer's disease: the two-hit hypothesis
    Xiongwei Zhu
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Lancet Neurol 3:219-26. 2004
    ..In this paper, we summarise evidence for oxidative stress and abnormal mitotic alterations in AD and explain the two-hit hypothesis by describing how both mechanisms are necessary and invariant features of disease...
  96. pmc Amyloid-beta in Alzheimer's disease: the horse or the cart? Pathogenic or protective?
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
    Int J Exp Pathol 86:133-8. 2005
    ..Thus, in this review, we discuss the role of amyloid-beta in the pathogenesis of AD and provide an alternative view to the widely accepted dogma...
  97. pmc Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Am J Pathol 173:470-82. 2008
    ..We further demonstrate that elevated oxidative stress and increased amyloid beta production are likely the potential pathogenic factors that cause DLP1 reduction and abnormal mitochondrial distribution in AD cells...
  98. pmc Leptin reduces Alzheimer's disease-related tau phosphorylation in neuronal cells
    Steven J Greco
    Neurotez Inc, Bridgewater, NJ, USA
    Biochem Biophys Res Commun 376:536-41. 2008
    ..Thus, leptin, which ameliorates both amyloid beta and tau-related pathological pathways, holds promise as a novel therapeutic for Alzheimer's disease...
  99. ncbi request reprint Will preventing protein aggregates live up to its promise as prophylaxis against neurodegenerative diseases?
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Brain Pathol 13:630-8. 2003
    ..In this review, we weigh the evidence of whether removal of amyloids, aggregates and neuronal inclusions represent a reasonable strategy for protecting neurons...
  100. ncbi request reprint Amyloid-beta, BACE, and oxidative stress in Alzheimer's disease, a commentary on "The different aggregation state of beta-amyloid 1-42 mediates different effects on oxidative stress, neurodegeneration and BACE-1 expression"
    Hyoung gon Lee
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Free Radic Biol Med 41:188-9. 2006
  101. ncbi request reprint Neuropathology of Alzheimer disease: pathognomonic but not pathogenic
    Rudy J Castellani
    Department of Pathology Neuropathology, University of Maryland, Baltimore, MD, USA
    Acta Neuropathol 111:503-9. 2006
    ....

Research Grants7

  1. Metal Ion is Critical in amyloid beta Induced JNK Activation
    Xiongwei Zhu; Fiscal Year: 2007
    ..Aim 3: Determine the effect of metal ion chelation on Ab-induced JNK activation. Aim 4: Determine whether H2O2 mediates metal-augmented AB-induced JNK activation. ..
  2. Mitochondrial Fission and Fusion in Alzheimer Disease
    Xiongwei Zhu; Fiscal Year: 2009
    ....
  3. Metal Ion is Critical in amyloid beta Induced JNK Activation
    Xiongwei Zhu; Fiscal Year: 2009
    ..Aim 3: Determine the effect of metal ion chelation on Ab-induced JNK activation. Aim 4: Determine whether H2O2 mediates metal-augmented AB-induced JNK activation. ..
  4. Mitochondrial Fission and Fusion in Alzheimer Disease
    Xiongwei Zhu; Fiscal Year: 2010
    ....