Roberto Cappai

Summary

Affiliation: University of Melbourne
Country: Australia

Publications

  1. 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
  2. doi request reprint 'From past to future' - deciphering the molecular basis of Alzheimer's disease through the pages of the Journal of Neurochemistry
    Roberto Cappai
    Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
    J Neurochem 139:215-223. 2016
  3. doi request reprint Combined deletions of amyloid precursor protein and amyloid precursor-like protein 2 reveal different effects on mouse brain metal homeostasis
    B Elise Needham
    Department of Pathology, The University of Melbourne, VIC 3010, Australia
    Metallomics 6:598-603. 2014
  4. doi request reprint Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments
    Laura J Vella
    Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
    FASEB J 26:2930-40. 2012
  5. ncbi request reprint Structural biology of prions
    Roberto Cappai
    Department of Pathology, University of Melbourne, Australia
    Contrib Microbiol 11:14-32. 2004
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Detail Information

Publications99

  1. 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...
  2. doi request reprint 'From past to future' - deciphering the molecular basis of Alzheimer's disease through the pages of the Journal of Neurochemistry
    Roberto Cappai
    Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
    J Neurochem 139:215-223. 2016
    ..The Journal of Neurochemistry has made significant contributions toward unraveling the molecular, cellular and pathological basis of Alzheimer's disease through its 60 years. This article is part of the 60th Anniversary special issue...
  3. doi request reprint Combined deletions of amyloid precursor protein and amyloid precursor-like protein 2 reveal different effects on mouse brain metal homeostasis
    B Elise Needham
    Department of Pathology, The University of Melbourne, VIC 3010, Australia
    Metallomics 6:598-603. 2014
    ..These studies identified age and genotype dependent changes in metal levels, and established differences in the relative roles played by APP and APLP2 in modulating metal homeostasis. ..
  4. doi request reprint Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments
    Laura J Vella
    Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
    FASEB J 26:2930-40. 2012
    ..These results identify a novel, developmentally regulated APP processing pathway that may play an important role in the physiological function of APP...
  5. ncbi request reprint Structural biology of prions
    Roberto Cappai
    Department of Pathology, University of Melbourne, Australia
    Contrib Microbiol 11:14-32. 2004
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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
    ....
  12. ncbi request reprint Alternative transcripts of presenilin-1 associated with frontotemporal dementia
    Genevieve Evin
    Department of Pathology, The University of Melbourne, and Mental Health Research Institute, Parkville, Victoria 3010, Australia
    Neuroreport 13:917-21. 2002
    ..RT-PCR analysis using nested primers showed the presence of PS1 gene products with deletions within the exon 4-8 region. Our results suggest that alternative transcription of PS1 may be associated with FTD...
  13. 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...
  14. 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...
  15. ncbi request reprint The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo
    Roberto Cappai
    Department of Pathology and Center for Neuroscience, The University of Melbourne, Victoria 3010, Australia
    J Biol Chem 280:13913-20. 2005
    ..These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1...
  16. pmc Metals and amyloid-beta in Alzheimer's disease
    Christa J Maynard
    Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Int J Exp Pathol 86:147-59. 2005
    ..Clinical trials are currently studying agents that can remedy abnormal Abeta-metal interactions...
  17. 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...
  18. doi request reprint Chronic exposure to high levels of zinc or copper has little effect on brain metal homeostasis or Abeta accumulation in transgenic APP-C100 mice
    Christa J Maynard
    Department of Pathology, The University of Melbourne, Melbourne, Vic, 3010, Australia
    Cell Mol Neurobiol 29:757-67. 2009
    ....
  19. pmc Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease
    Paul A Adlard
    Oxidation Biology Laboratory, The Mental Health Research Institute, Parkville, Victoria, Australia
    PLoS ONE 6:e17669. 2011
    ..In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function...
  20. 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...
  21. ncbi request reprint Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts
    Shayne A Bellingham
    Department of Genetics, The University of Melbourne, Victoria, Australia
    J Neurochem 91:423-8. 2004
    ....
  22. ncbi request reprint Neurotoxicity from glutathione depletion is mediated by Cu-dependent p53 activation
    Tai Du
    Department of Pathology, The University of Melbourne, Melbourne, VIC 3010, Australia
    Free Radic Biol Med 44:44-55. 2008
    ..These findings may have important implications for neurodegenerative disorders that involve GSH depletion and aberrant Cu metabolism...
  23. ncbi request reprint Diverse fibrillar peptides directly bind the Alzheimer's amyloid precursor protein and amyloid precursor-like protein 2 resulting in cellular accumulation
    Anthony R White
    Department of Pathology, The University of Melbourne, 3010, Victoria, Australia
    Brain Res 966:231-44. 2003
    ..These findings show that diverse fibrillogenic peptides can induce accumulation of APP and APLP2 and this mechanism could contribute to pathogenesis in neurodegenerative disorders...
  24. doi request reprint Mouse-adapted sporadic human Creutzfeldt-Jakob disease prions propagate in cell culture
    Victoria A Lawson
    Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Int J Biochem Cell Biol 40:2793-801. 2008
    ..Our observations underscore the likelihood that, in contrast to prions derived from non-human mammals, additional unidentified cofactors or subcellular environment are critical for the generation of human prions...
  25. 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...
  26. 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...
  27. 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...
  28. 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...
  29. doi request reprint Neurotoxicity of prion peptides on cultured cerebellar neurons
    Giuseppe D Ciccotosto
    Department of Pathology and Mental Health Research Institute of Victoria, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
    Methods Mol Biol 459:83-96. 2008
    ....
  30. doi 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...
  31. 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...
  32. doi request reprint A serial analysis of gene expression profile of the Alzheimer's disease Tg2576 mouse model
    Amee J George
    Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Parkville, VIC 3052, Australia
    Neurotox Res 17:360-79. 2010
    ..The novel approach of profiling the Tg2576 mouse brain using SAGE has identified different genes that could subsequently be examined for their potential as peripheral diagnostic and prognostic markers for Alzheimer's disease...
  33. 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...
  34. 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...
  35. 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...
  36. doi request reprint Conformational detection of prion protein with biarsenical labeling and FlAsH fluorescence
    Bradley M Coleman
    Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Biochem Biophys Res Commun 380:564-8. 2009
    ..This technique may also be applied to any protein that undergoes conformational change and/or misfolding such as those involved in other neurodegenerative disorders including Alzheimer's, Huntington's and Parkinson's diseases...
  37. 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...
  38. 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...
  39. doi request reprint Characterization of PiB binding to white matter in Alzheimer disease and other dementias
    Michelle T Fodero-Tavoletti
    Department of Pathology, University of Melbourne, and Department of Nuclear Medicine, Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia
    J Nucl Med 50:198-204. 2009
    ..Although the specificity of PiB for Abeta plaques in gray matter has been well described, the nature of PiB binding to white matter remains unclear. In this study, we characterized the binding of PiB to human white matter homogenates...
  40. doi request reprint Metallo-complex activation of neuroprotective signalling pathways as a therapeutic treatment for Alzheimer's disease
    Laura Bica
    Department of Pathology, The University of Melbourne, 3010, Victoria, Australia
    Mol Biosyst 5:134-42. 2009
    ..Further in vivo investigation is required to elucidate the mechanism of action of these metallo-complexes in vivo and determine their efficacy and safety as potential treatments of neurodegenerative diseases...
  41. ncbi request reprint Decreased phosphatidylethanolamine binding protein expression correlates with Abeta accumulation in the Tg2576 mouse model of Alzheimer's disease
    Amee J George
    Department of Pathology, University of Melbourne, Parkville 3010, Australia
    Neurobiol Aging 27:614-23. 2006
    ..Down-regulation of PEBP may result in lower levels of HCNP or altered coordination of signal transduction pathways that may contribute to neuronal dysfunction and pathogenesis in AD...
  42. 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...
  43. doi request reprint Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function
    Su Ling Leong
    The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
    Metallomics 6:105-16. 2014
    ..elegans. Overall, the data are consistent with a possible role in copper homeostasis for APP-D2, but not APL1-D2...
  44. ncbi request reprint Correlative studies support lipid peroxidation is linked to PrP(res) propagation as an early primary pathogenic event in prion disease
    Marcus W Brazier
    Department of Pathology, The University of Melbourne, VIC 3010, Australia
    Brain Res Bull 68:346-54. 2006
    ....
  45. ncbi request reprint Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology
    Christa J Maynard
    Department of Pathology, The University of Melbourne, VIC 3010, Australia
    J Inorg Biochem 100:952-62. 2006
    ..If depleting Cu and/or rising Mn levels contribute to AD pathogenesis, natural sex differences in these brain metal levels may contribute to the increased propensity of females to develop AD...
  46. 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...
  47. doi request reprint Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
    Peng Lei
    Mental Health Research Institute, The University of Melbourne, Victoria, Australia
    Nat Med 18:291-5. 2012
    ..These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer's disease, Parkinson's disease and tauopathies, and that it can be rescued pharmacologically...
  48. pmc Residues surrounding the glycosylphosphatidylinositol anchor attachment site of PrP modulate prion infection: insight from the resistance of rabbits to prion disease
    Rebecca M Nisbet
    Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia
    J Virol 84:6678-86. 2010
    ..However, these residues did inhibit PrP(Sc) formation, suggesting that these rabbit-specific residues interfere with a C-terminal PrP(Sc) interaction site...
  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. doi 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...
  51. 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...
  52. ncbi request reprint Expression of truncated presenilin 2 splice variant in Alzheimer's disease, bipolar disorder, and schizophrenia brain cortex
    Margaret J Smith
    Department of Pathology, The University of Melbourne, and The Mental Health Research Institute of Victoria, Grattan St, Parkville, Victoria 3010, Australia
    Brain Res Mol Brain Res 127:128-35. 2004
    ..Our findings support previous evidence for increased expression of this variant PS2 isoform in sporadic AD and suggest this isoform may contribute to neurodegeneration...
  53. doi request reprint Engineered antibody intervention strategies for Alzheimer's disease and related dementias by targeting amyloid and toxic oligomers
    Remy Robert
    CSIRO Molecular and Health Technologies, University of Melbourne, Australia
    Protein Eng Des Sel 22:199-208. 2009
    ..Hence, these recombinant antibody fragments represent attractive candidates and safer formulations of passive immunotherapy for AD...
  54. 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...
  55. 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...
  56. 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...
  57. doi request reprint A domain level interaction network of amyloid precursor protein and Abeta of Alzheimer's disease
    Victoria M Perreau
    Neuroproteomics and Neurogenomics Platform, National Neurosciences Facility, The University of Melbourne, Parkville, Vic, Australia
    Proteomics 10:2377-95. 2010
    ..Gene ontology and network analysis were used to identify potentially novel functional relationships among interacting proteins...
  58. doi request reprint In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies
    Michelle T Fodero-Tavoletti
    Department of Pathology, The University of Melbourne, Vic, Australia
    Eur J Pharmacol 617:54-8. 2009
    ..This study suggests that [(18)F]-BF227 is not Abeta-selective. Evaluation of BF227 as a potential biomarker for Parkinson's disease is warranted...
  59. pmc Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation
    Laura Bica
    Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
    PLoS ONE 9:e90070. 2014
    ....
  60. ncbi request reprint Overexpression of Alzheimer's disease amyloid-beta opposes the age-dependent elevations of brain copper and iron
    Christa J Maynard
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    J Biol Chem 277:44670-6. 2002
    ..These findings, complemented by our previous findings of elevated copper levels in APP knock-out mice, support roles for APP and Abeta in physiological metal regulation...
  61. doi request reprint In vitro characterization of [18F]-florbetaben, an Aβ imaging radiotracer
    Michelle T Fodero-Tavoletti
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    Nucl Med Biol 39:1042-8. 2012
    ..The objective of this study was to determine whether Florbetaben selectively binds to Aβ plaques in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and α-synuclein aggregates)...
  62. doi request reprint Modulation of alpha-synuclein aggregation by dopamine: a review
    Su Ling Leong
    Department of Pathology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia
    Neurochem Res 34:1838-46. 2009
    ..Here, we review the literature on the role of DA and its oxidative intermediates in modulating the aggregation pathways of alpha-syn...
  63. ncbi request reprint Selecting cells with different Alzheimer's disease gamma-secretase activity using FACS. Differential effect on presenilin exon 9 gamma- and epsilon-cleavage
    M Fleur Sernee
    Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
    Eur J Biochem 270:495-506. 2003
    ..The single aspartate mutations showed a concomitant reduction in Abeta secretion, whereas the D257A/D385A and DeltaE9 mutations had no effect on Abeta secretion...
  64. doi request reprint Gene knockout of tau expression does not contribute to the pathogenesis of prion disease
    Victoria A Lawson
    Department of Pathology, The University of Melbourne, Victoria, Australia
    J Neuropathol Exp Neurol 70:1036-45. 2011
    ....
  65. pmc The amyloid precursor protein copper binding domain histidine residues 149 and 151 mediate APP stability and metabolism
    Loredana Spoerri
    Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia
    J Biol Chem 287:26840-53. 2012
    ..These findings are of major significance for the design of novel AD therapeutic drugs targeting this APP domain...
  66. ncbi request reprint The role of exosomes in the processing of proteins associated with neurodegenerative diseases
    Laura J Vella
    Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010, Australia
    Eur Biophys J 37:323-32. 2008
    ..This review will be discussing the current literature regarding the role of exosomes in secretion of the proteins, PrP and APP, and the subsequent implications for neurodegenerative disease...
  67. ncbi request reprint Plasma alpha-synuclein is decreased in subjects with Parkinson's disease
    Qiao Xin Li
    Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
    Exp Neurol 204:583-8. 2007
    ..This initial study indicates that measurement of alphaSN in plasma can provide support for a clinical diagnosis of Parkinson's disease and warrants further study in a larger population...
  68. ncbi request reprint Amyloid imaging in Alzheimer's disease and other dementias
    Michelle T Fodero-Tavoletti
    Department of Pathology, The University of Melbourne, Melbourne, Victoria, 3010, Australia
    Brain Imaging Behav 3:246-61. 2009
    ....
  69. doi request reprint Alleviating transcriptional inhibition of the norepinephrine slc6a2 transporter gene in depolarized neurons
    K N Harikrishnan
    Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
    J Neurosci 30:1494-501. 2010
    ..These results now begin to offer a new perspective on the mechanism of Slc6a2 gene regulation...
  70. ncbi request reprint Alzheimer's disease amyloid beta and prion protein amyloidogenic peptides promote macrophage survival, DNA synthesis and enhanced proliferative response to CSF-1 (M-CSF)
    John A Hamilton
    Arthritis and Inflammation Research Centre, The University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Clinical Sciences Building, Royal Parade, Victoria 3050, Parkville, Australia
    Brain Res 940:49-54. 2002
    ..These fibrillogenic peptides join the list of aggregates having these effects on macrophages, indicating the generality of this type of response...
  71. ncbi request reprint Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein
    Anthony R White
    Department of Pathology, The University of Melbourne, Victoria 3010, Australia
    J Neurosci 22:365-76. 2002
    ..Our findings also suggest that targeting of inhibitors to histidine residues at positions 147 and 151 of APP could significantly alter the oxidative potential of APP...
  72. doi request reprint The ART of loss: Abeta imaging in the evaluation of Alzheimer's disease and other dementias
    Victor L Villemagne
    Department of Nuclear Medicine, Centre for PET, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia
    Mol Neurobiol 38:1-15. 2008
    ..Further longitudinal observations are required to confirm this hypothesis and to better elucidate the role of Abeta deposition in the course of Alzheimer's disease...
  73. 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
    ....
  74. doi request reprint Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid
    Laura J Vella
    Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia
    Vet Immunol Immunopathol 124:385-93. 2008
    ..This experimental approach suggests that CSF derived exosomes could be used as a novel means of detecting abnormal forms of the prion protein and provide an in vivo link between these vesicles and prion disease pathogenesis...
  75. doi request reprint Evidence for prion protein expression in enteroglial cells of the myenteric plexus of mouse intestine
    Valeria Albanese
    Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, Australia
    Auton Neurosci 140:17-23. 2008
    ..Our findings clearly indicate that EGCs of the mouse intestine constitutively express PrP(C); thus they could be a potential target for infectious prions...
  76. ncbi request reprint Neurotoxicity from glutathione depletion is dependent on extracellular trace copper
    Anthony R White
    Department of Pathology, The University of Melbourne, and The Mental Health Research Institute, Parkville, Victoria, Australia
    J Neurosci Res 71:889-97. 2003
    ..These studies demonstrate a critical role for extracellular trace copper in neuronal cell death caused by GSH depletion and may have important implications for the understanding of toxic processes in neurodegenerative diseases...
  77. ncbi request reprint Alternative transcripts of presenilin-1 associated with frontotemporal dementia
    Genevieve Evin
    Department of Pathology, The University of Melbourne, and Mental Health Research Institute, Parkville, Victoria 3010, Australia
    Neuroreport 13:719-23. 2002
    ..RT-PCR analysis using nested primers showed the presence of PS1 gene products with deletions within the exon 4-8 region. Our results suggest that alternative transcription of PS1 may be associated with FTD...
  78. ncbi request reprint Monitoring the prevention of amyloid fibril formation by alpha-crystallin. Temperature dependence and the nature of the aggregating species
    Agata Rekas
    Department of Chemistry, University of Wollongong, Australia
    FEBS J 274:6290-304. 2007
    ..It was shown that alphaB-crystallin interrupted alpha-synuclein aggregation at its earliest stages, most likely by binding to partially folded monomers and thereby preventing their aggregation into fibrillar structures...
  79. 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...
  80. ncbi request reprint Possible mechanisms of APP-mediated oxidative stress in Alzheimer's disease
    Gerd Multhaup
    ZMBH Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany
    Free Radic Biol Med 33:45-51. 2002
    ..APP itself binds Zn(II) and Cu(II) at nanomolar concentrations and an altered APP metabolism or expression level is believed to result in neurotoxic processes...
  81. ncbi request reprint Evidence for a copper-binding superfamily of the amyloid precursor protein
    Andreas Simons
    ZMBH Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, D 69120 Heidelberg, Germany
    Biochemistry 41:9310-20. 2002
    ..The more recently evolved homologues of human APP appear to take advantage of unique redox properties for yet unknown biological functions...
  82. ncbi request reprint Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2)
    Carlos Opazo
    Centro de Regulación Celular y Patología, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago 114 D, Chile
    J Biol Chem 277:40302-8. 2002
    ..Cu. Therefore, microregional catalytic H(2)O(2) production, combined with the exhaustion of reducing agents, may mediate the neurotoxicity of Abeta in Alzheimer's disease, and inhibitors of this novel activity may be of therapeutic value...
  83. 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...
  84. 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...
  85. 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
    ....
  86. 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...
  87. 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...
  88. 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...
  89. ncbi request reprint Alois Alzheimer and Alzheimer's disease: a centennial perspective
    David H Small
    Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
    J Neurochem 99:708-10. 2006
    ..In this article, we review the current status of the amyloid hypothesis of AD and its role in the development of future therapy...
  90. 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...
  91. ncbi request reprint Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11
    Olav M Andersen
    Max Delbrueck Center for Molecular Medicine, Berlin, 13125 Berlin, Germany
    Biochemistry 45:2618-28. 2006
    ..These data shed new light on the molecular determinants of neuronal APP trafficking and processing and on possible targets for intervention with senile plaque formation in patients with AD...
  92. 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...
  93. ncbi request reprint Clioquinol mediates copper uptake and counteracts copper efflux activities of the amyloid precursor protein of Alzheimer's disease
    Carina Treiber
    Freie Universitaet Berlin, Institut fuer Chemie Biochemie, Thielallee 63, D 14195 Berlin, Germany
    J Biol Chem 279:51958-64. 2004
    ..These data uncover a novel biological function for APP and APLP2 in copper efflux and provide a new conceptual framework for the formerly diverging theories of copper supplementation and chelation in the treatment of Alzheimer's disease...
  94. ncbi request reprint 6-Hydroxydopamine but not 1-methyl-4-phenylpyridinium abolishes alpha-synuclein anti-apoptotic phenotype by inhibiting its proteasomal degradation and by promoting its aggregation
    Cristine Alves da Costa
    IPMC du CNRS, UMR6097, Equipe Labellisée FRM, 660 route des Lucioles, 06560 Valbonne, France
    J Biol Chem 281:9824-31. 2006
    ..The drastically distinct effects of 6OH-DOPA and MPP(+) on alpha-synuclein function are discussed with respect to Parkinson disease pathology and animal models mimicking this pathology...
  95. doi request reprint ATP-binding cassette transporter A7 regulates processing of amyloid precursor protein in vitro
    Sharon L Chan
    Prince of Wales Medical Research Institute, Randwick, New South Wales, Australia
    J Neurochem 106:793-804. 2008
    ..These studies indicate that ABCA7 has the capacity to stimulate cellular cholesterol efflux to apoE discs and regulate APP processing resulting in an inhibition of Abeta production...
  96. ncbi request reprint Solution conformation and heparin-induced dimerization of the full-length extracellular domain of the human amyloid precursor protein
    Matthias Gralle
    Instituto de Bioquimica Medica, Programa de Bioquimica e Biofisica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944 590, Brazil
    J Mol Biol 357:493-508. 2006
    ..Possible implications of such complex formation for the physiological dimerization of APP and biological signaling are discussed in terms of the structural models proposed...
  97. pmc Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein
    Olav M Andersen
    Max Delbrueck Center for Molecular Medicine, D 13125 Berlin, Germany
    Proc Natl Acad Sci U S A 102:13461-6. 2005
    ..Consequently, reduced receptor expression in the human brain may increase Abeta production and plaque formation and promote spontaneous AD...
  98. 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...