Kevin J Barnham

Summary

Affiliation: University of Melbourne
Country: Australia

Publications

  1. ncbi request reprint Methylation of the imidazole side chains of the Alzheimer disease amyloid-beta peptide results in abolition of superoxide dismutase-like structures and inhibition of neurotoxicity
    Anna K Tickler
    Howard Florey Institute of Medical Research, Victoria 3010, Australia
    J Biol Chem 280:13355-63. 2005
  2. doi request reprint Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes
    Robyn A Sharples
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville Victoria 3010, Australia
    FASEB J 22:1469-78. 2008
  3. doi request reprint Metals in Alzheimer's and Parkinson's diseases
    Kevin J Barnham
    Bio21 Molecular Science and Biotechnology Institute, Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Curr Opin Chem Biol 12:222-8. 2008
  4. pmc The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease
    Lin W Hung
    The Mental Health Research Institute, The University of Melbourne, Victoria 3010 Australia
    J Exp Med 209:837-54. 2012
  5. pmc Alzheimer's disease and metals: a review of the involvement of cellular membrane receptors in metallosignalling
    Pavithra C Amadoruge
    Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, 30 Flemington Road, Parkville, VIC 3010, Australia
    Int J Alzheimers Dis 2011:542043. 2011
  6. ncbi request reprint Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease beta-amyloid
    Kevin J Barnham
    Department of Pathology, University of Melbourne, Victoria, Australia
    FASEB J 18:1427-9. 2004
  7. pmc Platinum-based inhibitors of amyloid-beta as therapeutic agents for Alzheimer's disease
    Kevin J Barnham
    Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia
    Proc Natl Acad Sci U S A 105:6813-8. 2008
  8. ncbi request reprint Neurotoxic, redox-competent Alzheimer's beta-amyloid is released from lipid membrane by methionine oxidation
    Kevin J Barnham
    Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Victoria 3010, Australia
    J Biol Chem 278:42959-65. 2003
  9. ncbi request reprint Enhanced toxicity and cellular binding of a modified amyloid beta peptide with a methionine to valine substitution
    Giuseppe D Ciccotosto
    Department of Pathology, University of Melbourne, Victoria 3010, Australia
    J Biol Chem 279:42528-34. 2004
  10. doi request reprint Formation of dopamine-mediated alpha-synuclein-soluble oligomers requires methionine oxidation
    Su Ling Leong
    Department of Pathology, The University of Melbourne, Parkville, Vic, Australia
    Free Radic Biol Med 46:1328-37. 2009

Detail Information

Publications95

  1. ncbi request reprint Methylation of the imidazole side chains of the Alzheimer disease amyloid-beta peptide results in abolition of superoxide dismutase-like structures and inhibition of neurotoxicity
    Anna K Tickler
    Howard Florey Institute of Medical Research, Victoria 3010, Australia
    J Biol Chem 280:13355-63. 2005
    ..This is consistent with the notion that Abeta-membrane interactions are important for neurotoxicity and that inhibiting these interactions has therapeutic potential...
  2. doi request reprint Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes
    Robyn A Sharples
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville Victoria 3010, Australia
    FASEB J 22:1469-78. 2008
    ..These results provide further evidence for a novel pathway in which APP fragments are released from cells and have implications for the analysis of APP processing and diagnostics for Alzheimer's disease...
  3. doi request reprint Metals in Alzheimer's and Parkinson's diseases
    Kevin J Barnham
    Bio21 Molecular Science and Biotechnology Institute, Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Curr Opin Chem Biol 12:222-8. 2008
    ..These small molecules show promise of being disease-modifying...
  4. pmc The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease
    Lin W Hung
    The Mental Health Research Institute, The University of Melbourne, Victoria 3010 Australia
    J Exp Med 209:837-54. 2012
    ..Our results show that Cu(II)(atsm) is effective in reversing parkinsonian defects in animal models and has the potential to be a successful treatment of PD...
  5. pmc Alzheimer's disease and metals: a review of the involvement of cellular membrane receptors in metallosignalling
    Pavithra C Amadoruge
    Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, 30 Flemington Road, Parkville, VIC 3010, Australia
    Int J Alzheimers Dis 2011:542043. 2011
    ..In this paper, the metal interactions with these membrane receptor systems will be explored and thus the potential for membrane receptors as an intervention point in AD will be assessed...
  6. ncbi request reprint Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease beta-amyloid
    Kevin J Barnham
    Department of Pathology, University of Melbourne, Victoria, Australia
    FASEB J 18:1427-9. 2004
    ..Confirming the theoretical results, mutation of the tyrosine residue to alanine inhibited H2O2 production, Cu-induced radicalization, dityrosine cross-linking, and neurotoxicity...
  7. pmc Platinum-based inhibitors of amyloid-beta as therapeutic agents for Alzheimer's disease
    Kevin J Barnham
    Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia
    Proc Natl Acad Sci U S A 105:6813-8. 2008
    ..The potent effect of the L-PtCl(2) complexes identifies this class of compounds as therapeutic agents for AD...
  8. ncbi request reprint Neurotoxic, redox-competent Alzheimer's beta-amyloid is released from lipid membrane by methionine oxidation
    Kevin J Barnham
    Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Victoria 3010, Australia
    J Biol Chem 278:42959-65. 2003
    ..We hypothesize that Met(O)Abeta production contributes to the elevation of soluble Abeta seen in the brain in Alzheimer's disease...
  9. ncbi request reprint Enhanced toxicity and cellular binding of a modified amyloid beta peptide with a methionine to valine substitution
    Giuseppe D Ciccotosto
    Department of Pathology, University of Melbourne, Victoria 3010, Australia
    J Biol Chem 279:42528-34. 2004
    ..These findings provide further evidence that the toxicity of Abeta is regulated by binding to neuronal cells...
  10. doi request reprint Formation of dopamine-mediated alpha-synuclein-soluble oligomers requires methionine oxidation
    Su Ling Leong
    Department of Pathology, The University of Melbourne, Parkville, Vic, Australia
    Free Radic Biol Med 46:1328-37. 2009
    ..Our study defines methionine oxidation as the dominant mechanism by which DA generates soluble alpha-synuclein oligomers and highlights the potential role for oxidative stress in modulating alpha-synuclein aggregation...
  11. pmc Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation
    Peter J Crouch
    Department of Pathology, Centre for Neuroscience, School of Chemistry, and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victorial, 3010, Australia
    Proc Natl Acad Sci U S A 106:381-6. 2009
    ..This study demonstrates that increasing intracellular copper bioavailability can restore cognitive function by inhibiting the accumulation of neurotoxic Abeta trimers and phosphorylated tau...
  12. doi request reprint Sustained activation of glial cell epidermal growth factor receptor by bis(thiosemicarbazonato) metal complexes is associated with inhibition of protein tyrosine phosphatase activity
    Katherine Ann Price
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    J Med Chem 52:6606-20. 2009
    ..These studies provide an important insight into the mechanism of action of a neuroprotective M(II)(btsc) and provide a basis for future studies into this novel approach to AD therapy...
  13. doi request reprint Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta
    Paul A Adlard
    Oxidation Biology Laboratory, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia
    Neuron 59:43-55. 2008
    ..The speed of recovery of the animals underscores the acutely reversible nature of the cognitive deficits associated with transgenic models of AD...
  14. doi request reprint Amyloid-beta peptide (Abeta) neurotoxicity is modulated by the rate of peptide aggregation: Abeta dimers and trimers correlate with neurotoxicity
    Lin Wai Hung
    Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Neurosci 28:11950-8. 2008
    ....
  15. doi request reprint Stereospecific interactions are necessary for Alzheimer disease amyloid-β toxicity
    Giuseppe D Ciccotosto
    Department of Pathology, The University of Melbourne, VIC 3010, Australia
    Neurobiol Aging 32:235-48. 2011
    ..This suggests that Aβ mediated toxicity in Alzheimer disease is dependent upon Aβ binding to phosphatidylserine on neuronal cells...
  16. ncbi request reprint Selective intracellular release of copper and zinc ions from bis(thiosemicarbazonato) complexes reduces levels of Alzheimer disease amyloid-beta peptide
    Paul S Donnelly
    School of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Biol Chem 283:4568-77. 2008
    ..However, a role for alternative metal-induced Abeta metabolism has not been ruled out. These studies demonstrate that MII(btsc) complexes have potential for Alzheimer disease therapy...
  17. ncbi request reprint Activation of epidermal growth factor receptor by metal-ligand complexes decreases levels of extracellular amyloid beta peptide
    Katherine A Price
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    Int J Biochem Cell Biol 40:1901-17. 2008
    ..These findings provide the first evidence that metal-ligand complexes can activate the epidermal growth factor receptor with potentially neuroprotective effects...
  18. ncbi request reprint Methionine regulates copper/hydrogen peroxide oxidation products of Abeta
    Feda E Ali
    School of Chemistry, University of Melbourne, VIC 3010, Australia
    J Pept Sci 11:353-60. 2005
    ..Similar products could be formed from the oxidation of Met(35) of Abeta and may relate to changes in properties of the peptide following MCO...
  19. ncbi request reprint Amyloid-beta peptide disruption of lipid membranes and the effect of metal ions
    Tong Lay Lau
    School of Chemistry, The University of Melbourne, Melbourne, VIC 3010, Australia
    J Mol Biol 356:759-70. 2006
    ..Incorporated peptides appear to disrupt the membrane more severely than associated peptides, which may have implications for the role of Abeta in disease states...
  20. doi request reprint Bis(thiosemicarbazonato) Cu-64 complexes for positron emission tomography imaging of Alzheimer's disease
    Michelle T Fodero-Tavoletti
    Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia
    J Alzheimers Dis 20:49-55. 2010
    ..This approach has the potential to offer complementary information to other diagnostic procedures that elucidate plaque burden...
  21. doi request reprint The Alzheimer's therapeutic PBT2 promotes amyloid-β degradation and GSK3 phosphorylation via a metal chaperone activity
    Peter J Crouch
    Department of Pathology, The University of Melbourne, Victoria, Australia
    J Neurochem 119:220-30. 2011
    ..Intracellular translocation of Zn and Cu via the metal chaperone activity of PBT2 may be an important mechanism by which PBT2 improves cognitive function in people with AD...
  22. pmc Conservation of a glycine-rich region in the prion protein is required for uptake of prion infectivity
    Christopher F Harrison
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Biol Chem 285:20213-23. 2010
    ..These data suggest that this region of PrP(C) is critical in the misfolding process and could serve as a novel, species-independent target for prion disease therapeutics...
  23. doi request reprint Dopamine and the dopamine oxidation product 5,6-dihydroxylindole promote distinct on-pathway and off-pathway aggregation of alpha-synuclein in a pH-dependent manner
    Chi L L Pham
    Department of Pathology, The University of Melbourne, Victoria, Australia
    J Mol Biol 387:771-85. 2009
    ..These results suggest that distinct reactive intermediates of DA, and not DA itself, interact with alpha-syn to generate the alpha-syn aggregates implicated in Parkinson's disease...
  24. pmc Diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)) protects against peroxynitrite-induced nitrosative damage and prolongs survival in amyotrophic lateral sclerosis mouse model
    Cynthia P W Soon
    Department of Pathology, Mental Health Research Institute, School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia
    J Biol Chem 286:44035-44. 2011
    ..CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS...
  25. doi request reprint Dominant roles of the polybasic proline motif and copper in the PrP23-89-mediated stress protection response
    Cathryn L Haigh
    Department of Pathology, The University of Melbourne, 3010, Australia
    J Cell Sci 122:1518-28. 2009
    ..Our findings show that N2 is a biologically active fragment that is able to modulate stress-induced intracellular ROS through interaction of its structurally defined N-terminal polybasic region with cell-surface proteoglycans...
  26. pmc Anionic phospholipid interactions of the prion protein N terminus are minimally perturbing and not driven solely by the octapeptide repeat domain
    Martin P Boland
    Department of Pathology, University of Melbourne, Parkville 3010, Australia
    J Biol Chem 285:32282-92. 2010
    ..Potential functional implications related to cellular stress responses are discussed...
  27. doi request reprint Histidine 14 modulates membrane binding and neurotoxicity of the Alzheimer's disease amyloid-beta peptide
    Danielle G Smith
    Department of Pathology, The University of Melbourne Parkville, Victoria, Australia
    J Alzheimers Dis 19:1387-400. 2010
    ..Our data suggests that it is the imidazole sidechain of histidine 14 that modulates this interaction and strategies inhibiting this interaction may have therapeutic potential for Alzheimer's disease...
  28. ncbi request reprint Cu2+ binding modes of recombinant alpha-synuclein--insights from EPR spectroscopy
    Simon C Drew
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    J Am Chem Soc 130:7766-73. 2008
    ..In total, four Cu(2+) binding modes were identified within pH 5.0-7.4, providing a more comprehensive picture of the Cu(2+) binding properties of recombinant alphaS...
  29. ncbi request reprint Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge
    David P Smith
    Department of Pathology, Centre for Neuroscience, and School of Chemistry, University of Melbourne, Victoria 3010, Australia
    J Biol Chem 281:15145-54. 2006
    ..These findings indicate that the generation of the Abeta toxic species is modulated by the Cu2+ concentration and the ability to form an intermolecular His bridge...
  30. pmc Pathogenic mutations within the hydrophobic domain of the prion protein lead to the formation of protease-sensitive prion species with increased lethality
    Bradley M Coleman
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia
    J Virol 88:2690-703. 2014
    ..This study highlights a certain region of the prion protein as being involved in this effect and demonstrates that prions are not always resistant to protease treatment...
  31. ncbi request reprint Cholesterol and Clioquinol modulation of A beta(1-42) interaction with phospholipid bilayers and metals
    Tong Lay Lau
    School of Chemistry, Bio21 Institute, The University of Melbourne, Victoria 3010, Australia
    Biochim Biophys Acta 1768:3135-44. 2007
    ..The results are consistent with oligomeric beta-sheet structured peptides only partially penetrating the bilayer and cholesterol reducing the membrane disruption...
  32. pmc Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands
    Aphrodite Caragounis
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    Biochem J 407:435-50. 2007
    ..Given that a structurally diverse array of ligands was assessed, the results are consistent with the effects being due to metal transport rather than the chelating ligand interacting directly with a receptor...
  33. doi request reprint Formation of a high affinity lipid-binding intermediate during the early aggregation phase of alpha-synuclein
    David P Smith
    Department of Pathology, The University of Melbourne, Victoria, 3010, Australia
    Biochemistry 47:1425-34. 2008
    ..Oligomeric alpha-syn is known to be toxic, and it is feasible that the high affinity binding species described here may correspond to a toxic species involved in PD...
  34. ncbi request reprint Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in Alzheimer's disease
    Carlos Opazo
    Oxidation Disorders Laboratory, Mental Health Research Institute of Victoria, and Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
    Aging Cell 5:69-79. 2006
    ..These data support metallated Abeta species as the neuropharmacological target of CQ and indicate that this drug class may have potential as in vivo imaging agents for Alzheimer neuropathology...
  35. ncbi request reprint Therapeutic treatments for Alzheimer's disease based on metal bioavailability
    Peter J Crouch
    Department of Pathology, University of Melbourne, Victoria 3010, Australia
    Drug News Perspect 19:469-74. 2006
    ..The metal ligand clioquinol has been used successfully in vitro, as well as in animal models and small clinical trials, and a new generation of metal ligand-based therapeutics is under development...
  36. doi request reprint Cell cycle arrest in cultured neuroblastoma cells exposed to a bis(thiosemicarbazonato) metal complex
    Laura Bica
    Department of Pathology, The University of Melbourne, Melbourne, VIC 3010, Australia
    Biometals 24:117-33. 2011
    ..Further studies are needed to examine the therapeutic potential of Cu(II)(gtsm) and other bis(thiosemicarbazonato) metal complexes as metallo-drugs for treatment of systemic or brain tumors...
  37. ncbi request reprint A copper radiopharmaceutical for diagnostic imaging of Alzheimer's disease: a bis(thiosemicarbazonato)copper(II) complex that binds to amyloid-beta plaques
    SinChun Lim
    School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia 3010
    Chem Commun (Camb) 46:5437-9. 2010
    ..The complex has the potential to be of use as a copper-64 radiopharmaceutical to assist in the diagnosis of Alzheimer's disease by positron emission tomography...
  38. ncbi request reprint Membrane interactions and the effect of metal ions of the amyloidogenic fragment Abeta(25-35) in comparison to Abeta(1-42)
    Tong Lay Lau
    School of Chemistry, Bio21 Institute, The University of Melbourne, VIC 3010, Australia
    Biochim Biophys Acta 1768:2400-8. 2007
    ..Since the Abeta(25-35) fragment is also neurotoxic, the full-length peptide may have more than one pathway for toxicity...
  39. doi request reprint Copper and zinc bis(thiosemicarbazonato) complexes with a fluorescent tag: synthesis, radiolabelling with copper-64, cell uptake and fluorescence studies
    SinChun Lim
    School of Chemistry, University of Melbourne, Parkville, Vic, 3010, Australia
    J Biol Inorg Chem 15:225-35. 2010
    ..In both cases, there was no evidence of uptake of the copper(II) bis(thiosemicarbazonato) complexes in the area of the cell nucleus...
  40. pmc Near-infrared fluorescence imaging of apoptotic neuronal cell death in a live animal model of prion disease
    Victoria A Lawson
    Department of Pathology, University of Melbourne, Victoria 3010, Australia Mental Health Research Institute, Parkville, Victoria 352, Australia
    ACS Chem Neurosci 1:720-7. 2010
    ..The contrast agent and related analogues will enable the longitudinal study of disease progression and therapy in animal models of many neurodegenerative conditions...
  41. doi request reprint Optical imaging detects apoptosis in the brain and peripheral organs of prion-infected mice
    Simon C Drew
    Department of Pathology, Neuroproteomics Platform National Neuroscience Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia
    J Neuropathol Exp Neurol 70:143-50. 2011
    ....
  42. doi request reprint Restored degradation of the Alzheimer's amyloid-beta peptide by targeting amyloid formation
    Peter J Crouch
    Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
    J Neurochem 108:1198-207. 2009
    ..This provides new data indicating that therapeutic compounds designed to modulate Abeta-metal interactions can inhibit Abeta accumulation by restoring the catalytic potential of Abeta-degrading proteases...
  43. ncbi request reprint The redox chemistry of the Alzheimer's disease amyloid beta peptide
    Danielle G Smith
    Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Biochim Biophys Acta 1768:1976-90. 2007
    ..Similarly, natural antioxidants curcumin and ginkgo extract have modest but positive effects in slowing AD development. Therefore, drugs that target the oxidative pathways in AD could have genuine therapeutic efficacy...
  44. ncbi request reprint Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway
    Roberto Cappai
    Department of Pathology, The University of Melbourne, Victoria, Australia
    FASEB J 19:1377-9. 2005
    ..These observations support the paradigm emerging for other neurodegenerative diseases that the toxic species is represented by a soluble oligomer and not the insoluble fibril...
  45. doi request reprint Mixed ligand Cu2+ complexes of a model therapeutic with Alzheimer's amyloid-β peptide and monoamine neurotransmitters
    Vijaya B Kenche
    Mental Health Research Institute, The University of Melbourne, Victoria 3010, Australia
    Inorg Chem 52:4303-18. 2013
    ..Our findings suggest a molecular basis for the strong metal chaperone activity of PBT2, its ability to attenuate Cu(2+)/Aβ interactions, and its potential to promote neuroprotective and neuroregenerative effects...
  46. doi request reprint Increasing the predictive accuracy of amyloid-β blood-borne biomarkers in Alzheimer's disease
    Andrew D Watt
    Department of Pathology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia
    J Alzheimers Dis 24:47-59. 2011
    ..Furthermore, the findings indicate that the incorporation of non-amyloid markers into predictive models, function to increase the accuracy of the diagnostic potential of Aβ...
  47. pmc Alzheimer's Aβ peptides with disease-associated N-terminal modifications: influence of isomerisation, truncation and mutation on Cu2+ coordination
    Simon C Drew
    Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
    PLoS ONE 5:e15875. 2010
    ..In particular, Aβ in plaques contain a significant amount of truncated pyroglutamate species, which appear to correlate with disease progression...
  48. ncbi request reprint Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent up-regulation of metalloprotease activity
    Anthony R White
    Department of Pathology, University of Melbourne, Cnr Grattan Street and Royal Parade, Victoria 3010, Australia
    J Biol Chem 281:17670-80. 2006
    ..Our findings identify an alternative mechanism of action for CQ in the reduction of Abeta deposition in the brains of CQ-treated animals and potentially in Alzheimer disease patients...
  49. pmc Stabilization of neurotoxic soluble beta-sheet-rich conformations of the Alzheimer's disease amyloid-beta peptide
    Deborah J Tew
    Department of Pathology, Centre for Neuroscience, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
    Biophys J 94:2752-66. 2008
    ..These SDS-induced beta-sheet forms of Abeta, both in the presence and absence of Cu(2+), are toxic to neuronal cells...
  50. pmc Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease
    James A Duce
    Mental Health Research Institute, The University of Melbourne, Parkville, Victoria 3052, Australia
    Cell 142:857-67. 2010
    ..Abnormal exchange of cortical zinc may link amyloid pathology with neuronal iron accumulation in AD...
  51. ncbi request reprint Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-beta peptide--relevance to N-terminally truncated forms
    Simon C Drew
    Department of Pathology and Neuroproteomics Platform, National Neuroscience Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
    J Am Chem Soc 131:8760-1. 2009
    ....
  52. ncbi request reprint Concentration dependent Cu2+ induced aggregation and dityrosine formation of the Alzheimer's disease amyloid-beta peptide
    David P Smith
    Department of Pathology, The University of Melbourne, Victoria, 3010, Australia
    Biochemistry 46:2881-91. 2007
    ..These results define the role Cu2+ plays in modulating the aggregation state and toxicity of Abeta1-42...
  53. pmc Utility of an improved model of amyloid-beta (Aβ₁₋₄₂) toxicity in Caenorhabditis elegans for drug screening for Alzheimer's disease
    Gawain McColl
    The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria 3010, Australia
    Mol Neurodegener 7:57. 2012
    ..Ease of culturing and a short life cycle make this animal model well suited to rapid screening of candidate compounds...
  54. ncbi request reprint Iron inhibits neurotoxicity induced by trace copper and biological reductants
    Anthony R White
    Department of Pathology and Centre for Neuroscience, The University of Melbourne, 3010, Carlton South, Victoria, Australia
    J Biol Inorg Chem 9:269-80. 2004
    ..These findings have important implications for trace biometal interactions and free radical-mediated damage during neurodegenerative illnesses such as Alzheimer's disease and old-age dementia...
  55. pmc The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease
    Victor A Streltsov
    Commonwealth Scientific Industrial Research Organization Molecular and Health Technologies, and Preventative Health Flagship, Parkville, Victoria 3052, Australia
    Biophys J 95:3447-56. 2008
    ..The structure of the high-affinity Cu(2+) binding site is consistent with the hypothesis that the redox activity of the metal ion bound to Abeta can lead to the formation of dityrosine-linked dimers found in AD...
  56. ncbi request reprint Dimerisation of N-acetyl-L-tyrosine ethyl ester and Abeta peptides via formation of dityrosine
    Feda E Ali
    School of Chemistry, University of Melbourne, Vic, 3010, Australia
    Free Radic Res 40:1-9. 2006
    ..We also report a simple fluorescent plate reader method for monitoring Abeta dimerisation via dityrosine formation...
  57. doi request reprint Amyloid-β: the seeds of darkness
    Michelle T Fodero-Tavoletti
    Department of Pathology, Bio21 Molecular and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia
    Int J Biochem Cell Biol 43:1247-51. 2011
    ..Although Alzheimer's disease remains incurable, improvements to Aβ immunotherapies and strategies to target Aβ continue to evolve, with the reliance upon Aβ imaging to shed light on the outcome of therapeutics proving very useful...
  58. ncbi request reprint Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42
    Peter J Crouch
    Centre for Neuroscience, The University of Melbourne, Victoria 3010, Australia
    J Neurosci 25:672-9. 2005
    ..We conclude that Cu2+-dependent Abeta-mediated inhibition of COX may be an important contributor to the neurodegeneration process in Alzheimer's disease...
  59. ncbi request reprint Copper-dependent inhibition of cytochrome c oxidase by Abeta(1-42) requires reduced methionine at residue 35 of the Abeta peptide
    Peter J Crouch
    Centre for Neuroscience, The University of Melbourne, Victoria, Australia
    J Neurochem 99:226-36. 2006
    ..We propose that amyloid-beta-mediated inhibition of cytochrome oxidase is dependent on the peptide's capacity to bind, then reduce Cu2+, and that it may involve the formation of a redox active amyloid-beta-methionine radical...
  60. doi request reprint Pleomorphic copper coordination by Alzheimer's disease amyloid-beta peptide
    Simon C Drew
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    J Am Chem Soc 131:1195-207. 2009
    ....
  61. doi request reprint Pharmacotherapeutic targets in Alzheimer's disease
    Yif at Biran
    The Oxidation Biology Laboratory, The Mental Health Research Institute, Parkville, Victoria, Australia
    J Cell Mol Med 13:61-86. 2009
    ..We will review the way these pharmacological strategies target the biochemical and clinical features of the disease and the investigational drugs for each category...
  62. ncbi request reprint Delineating common molecular mechanisms in Alzheimer's and prion diseases
    Kevin J Barnham
    Department of Pathology, and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia
    Trends Biochem Sci 31:465-72. 2006
    ..Key sequence and chemical similarities between prion protein (PrP) and Abeta indicate that similar therapeutic strategies might be applicable for the treatment of Alzheimer's and prion diseases...
  63. pmc Alzheimer's disease & metals: therapeutic opportunities
    Vijaya B Kenche
    The Mental Health Research Institute, The University of Melbourne, Parkville, Vic, Australia
    Br J Pharmacol 163:211-9. 2011
    ..The success of these various strategies suggests that manipulating metal ion interactions offers multiple opportunities to develop disease modifying therapies for AD...
  64. doi request reprint 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease
    Michelle T Fodero-Tavoletti
    Department of Pathology, The University of Melbourne, Victoria, 3010, Australia
    Brain 134:1089-100. 2011
    ..The preclinical examination of THK523 has demonstrated its high affinity and selectivity for tau pathology both in vitro and in vivo, indicating that (18)F-THK523 fulfils ligand criteria for human imaging trials...
  65. ncbi request reprint Neurotoxicity in Alzheimer's disease: is covalently crosslinked A beta responsible?
    Ryan Naylor
    Department of Pathology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia
    Eur Biophys J 37:265-8. 2008
    ..These findings offer new avenues for the treatment and prevention of disease, by modulating metal binding or preventing the formation of neurotoxic A beta oligomers...
  66. ncbi request reprint Metal ions, pH, and cholesterol regulate the interactions of Alzheimer's disease amyloid-beta peptide with membrane lipid
    Cyril C Curtain
    Department of Pathology, University of Melbourne, Victoria 3052, Australia
    J Biol Chem 278:2977-82. 2003
    ..Peptides that did not insert into the membrane formed beta-sheet structures on the surface of the lipid...
  67. doi request reprint Electron paramagnetic resonance characterization of the copper-resistance protein PcoC from Escherichia coli
    Simon C Drew
    Department of Pathology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia
    J Biol Inorg Chem 13:899-907. 2008
    ..The markedly different spectra of the H1F and nA forms compared with the wild-type and H92F proteins further highlight the integral role of the N-terminal histidine residue in the high-affinity Cu(II) site of PcoC...
  68. ncbi request reprint In vitro characterization of Pittsburgh compound-B binding to Lewy bodies
    Michelle T Fodero-Tavoletti
    Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia
    J Neurosci 27:10365-71. 2007
    ..These studies indicate that PIB retention observed within the cortical gray matter regions of DLB subjects in [11C]-PIB PET studies is largely attributable to PIB binding to Abeta plaques and not Lewy bodies...
  69. ncbi request reprint Metal catalyzed oxidation of tyrosine residues by different oxidation systems of copper/hydrogen peroxide
    Feda E Ali
    School of Chemistry, University of Melbourne, Melbourne, VIC 3010, Australia
    J Inorg Biochem 98:173-84. 2004
    ..The results showed that DT formation could be observed upon Cu2+/H2O2 oxidation at pH 7.4. Our results indicate that it is unlikely to be via Fenton chemistry since Cu+/H2O2 oxidative conditions did not lead to the formation of DT...
  70. ncbi request reprint Characterizing bathocuproine self-association and subsequent binding to Alzheimer's disease amyloid beta-peptide by NMR
    Shenggen Yao
    The Walter and Eliza Hall Institute of Medical Research, and The Cooperative Research Center for Cellular Growth Factors, 1G Royal Parade, Parkville, VIC 3050, Australia
    J Pept Sci 10:210-7. 2004
    ..From the self-association constant of BC, Ka, the fraction of dimeric BC in the complex was obtained and the dissociation constant, Kd, of BC bound to A beta40 peptide was then determined to be approximately 1 mM...
  71. ncbi request reprint Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis
    Kevin J Barnham
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    J Biol Chem 278:17401-7. 2003
    ..The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter...
  72. ncbi request reprint Analysis of Abeta interactions using ProteinChip technology
    Eleni Giannakis
    Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia
    Methods Mol Biol 494:71-86. 2008
    ..These include analyzing (1) Abeta processing and quantitation of peptide fragments, (2) Abeta aggregation and the quantitation of oligomers, and (3) Abeta-lipid interactions...
  73. pmc The Caenorhabditis elegans A beta 1-42 model of Alzheimer disease predominantly expresses A beta 3-42
    Gawain McColl
    Mental Health Research Institute, Parkville, Victoria 3052, Australia
    J Biol Chem 284:22697-702. 2009
    ..Although unexpected, the C. elegans model of A beta expression can now be co-opted to study the proteotoxic effects and processing of A beta(3-42)...
  74. ncbi request reprint Metal homeostasis in Alzheimer's disease
    Anthony R White
    The University of Melbourne, Department of Pathology, Victoria 3010, Australia
    Expert Rev Neurother 6:711-22. 2006
    ..This information will be vital for the development of safe and effective metal-based pharmaceuticals for the treatment of AD and, potentially, other neurodegenerative disorders...
  75. ncbi request reprint Delineating the mechanism of Alzheimer's disease A beta peptide neurotoxicity
    Roberto Cappai
    Department of Pathology, The University of Melbourne, Melbourne, VIC 3010, Australia
    Neurochem Res 33:526-32. 2008
    ..This mechanism by which A beta mediates neurotoxicity or neuronal dysfunction is not fully resolved. This review will outline some of the key determinants that modulate A beta's activity and the cellular pathways and mechanisms involved...
  76. ncbi request reprint Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics
    Colin L Masters
    Department of Pathology, The University of Melbourne, Vic, Australia
    J Neurochem 97:1700-25. 2006
    ....
  77. ncbi request reprint Neurodegenerative diseases and oxidative stress
    Kevin J Barnham
    Department of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Victoria 3010, Australia
    Nat Rev Drug Discov 3:205-14. 2004
    ..However, this same complexity provides a number of therapeutic targets, and different strategies, including novel metal-protein attenuating compounds, aimed at a variety of targets have shown promise in clinical studies...
  78. ncbi request reprint Neurotoxic species in prion disease: a role for PrP isoforms?
    Christopher F Harrison
    Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
    J Neurochem 103:1709-20. 2007
    ..In this study, we review current knowledge on neurotoxic PrP species, including the importance of a central hydrophobic domain for mediating neurotoxicty...
  79. ncbi request reprint Structure and activity of D-Pro14 melittin
    Dean R Hewish
    CSIRO Health Sciences and Nutrition, Parkville Laboratory, Victoria, Australia
    J Protein Chem 21:243-53. 2002
    ..Electron-paramagnetic resonance studies suggest that there is a positive correlation between hemolytic activity of the peptides and interaction with phospholipid bilayers...
  80. doi request reprint Biophysical investigations of the prion protein using electron paramagnetic resonance
    Simon C Drew
    Department of Pathology and Mental Health Research Institute of Victoria, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
    Methods Mol Biol 459:173-96. 2008
    ..An overview of the EPR technique as applied to the prion protein is given, key results are summarized, and some future experimental avenues are outlined...
  81. doi request reprint Blood-borne amyloid-beta dimer correlates with clinical markers of Alzheimer's disease
    Victor L Villemagne
    Mental Health Research Institute, The University of Melbourne, Parkville, Melbourne, Victoria 3052, Australia
    J Neurosci 30:6315-22. 2010
    ..These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD...
  82. ncbi request reprint Structural studies of the Alzheimer's amyloid precursor protein copper-binding domain reveal how it binds copper ions
    Geoffrey K W Kong
    Biota Structural Biology Laboratory, St Vincent s Institute, 9 Princes Street, Fitzroy, Victoria 3065, Australia
    J Mol Biol 367:148-61. 2007
    ..The geometry of the site is unfavorable for Cu(+), thus providing a mechanism by which CuBD could readily transfer Cu ions to other proteins...
  83. pmc Copper binding to the Alzheimer's disease amyloid precursor protein
    Geoffrey K W Kong
    Biota Structural Biology Laboratory, St Vincent s Institute of Medical Research, 9 Princes Street, Fitzroy, VIC 3065, Australia
    Eur Biophys J 37:269-79. 2008
    ..We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer's disease...
  84. pmc Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer's disease
    Geoffrey K W Kong
    Biota Structural Biology Laboratory, St Vincent s Institute, Fitzroy, Victoria 3065, Australia
    Acta Crystallogr Sect F Struct Biol Cryst Commun 61:93-5. 2005
    ..The crystallization of CuBD in two different forms suitable for structure determination is reported here...
  85. doi request reprint Amyloid-beta-anti-amyloid-beta complex structure reveals an extended conformation in the immunodominant B-cell epitope
    Luke A Miles
    Biota Structural Biology Laboratory, St Vincent s Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia
    J Mol Biol 377:181-92. 2008
    ..Thus, antibodies that target the N-terminal region of A beta, such as WO2, hold promise for therapeutic development...
  86. ncbi request reprint Biological activity and ferric ion binding of fragments of glycine-extended gastrin
    Hong He
    The University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria 3084, Australia
    Biochemistry 43:11853-61. 2004
    ..These observations indicate that extensive proteolytic processing may not completely inactivate Ggly and that bioactive forms that are not detected by current radioimmunoassays may be present in tissues and/or plasma...
  87. pmc Alzheimer disease beta-amyloid activity mimics cholesterol oxidase
    Luigi Puglielli
    Neurobiology of Disease Laboratory, Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
    J Clin Invest 115:2556-63. 2005
    ..Cu2+-mediated oxidation of cholesterol may be a pathogenic mechanism common to atherosclerosis and AD...
  88. ncbi request reprint Cu2+-induced modification of the kinetics of A beta(1-42) channels
    Randa Bahadi
    Membrane Transport Group, Department of Chemistry, The Faculties, The Australian National University, Canberra, Australian Capital Territory 0200, Australia
    Am J Physiol Cell Physiol 285:C873-80. 2003
    ....
  89. ncbi request reprint Model studies of cholesterol and ascorbate oxidation by copper complexes: relevance to Alzheimer's disease beta-amyloid metallochemistry
    Fredrik Haeffner
    Physics Department, Virginia Commonwealth University, Richmond, VA 23284, USA
    J Inorg Biochem 99:2403-22. 2005
    ..DFT also predicted that Abeta will cross-link via covalent dityrosine formation during the oxidation of ascorbate but not during the oxidation of cholesterol. Experimental data were consistent with these predictions...
  90. pmc Crystallization and preliminary X-ray diffraction analysis of the Fab fragment of WO2, an antibody specific for the Abeta peptides associated with Alzheimer's disease
    Kwok S Wun
    Biota Structural Biology Laboratory and Centre for Structural Neurobiology, St Vincent s Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
    Acta Crystallogr Sect F Struct Biol Cryst Commun 64:438-41. 2008
    ..6 A resolution. A second crystal form of WO2 Fab was grown in the presence of the sparingly soluble Abeta(1-42) in PEG 550 MME. This second form belonged to space group P2(1) and diffracted to 1.9 A resolution...
  91. pmc Surface behavior and lipid interaction of Alzheimer beta-amyloid peptide 1-42: a membrane-disrupting peptide
    Ernesto E Ambroggio
    CIQUIBIC CONICET, Departamento de Quimica Biologica, Facultad de Ciencias Quimicas, Ciudad Universitaria, Córdoba CP 5000, Argentina
    Biophys J 88:2706-13. 2005
    ....
  92. ncbi request reprint Structure of a novel P-superfamily spasmodic conotoxin reveals an inhibitory cystine knot motif
    Luke A Miles
    The Walter and Eliza Hall Institute of Medical Research, NMR Laboratory, 381 Royal Parade, Parkville 3052, Australia
    J Biol Chem 277:43033-40. 2002
    ....
  93. ncbi request reprint Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity
    Agata Rekas
    Department of Chemistry, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia
    J Mol Biol 340:1167-83. 2004
    ..In summary, alpha-synuclein and alphaB-crystallin interact readily with each other and affect each other's properties, in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone action...
  94. doi request reprint Dimeric structures of alpha-synuclein bind preferentially to lipid membranes
    Eleni Giannakis
    The Howard Florey Institute of Medical Research, Australia
    Biochim Biophys Acta 1778:1112-9. 2008
    ..These data collectively indicate that the dimeric species of Wt and its mutants can bind and cause membrane perturbations...
  95. ncbi request reprint Ferric ions are essential for the biological activity of the hormone glycine-extended gastrin
    Julie Pannequin
    University of Melbourne Department of Surgery, Austin Campus, ARMC, Heidelberg, Victoria 3084, Australia
    J Biol Chem 277:48602-9. 2002
    ..This is the first report of an essential role for a metal ion in the action of a hormone...