Research Topics
| J McLaurinSummaryAffiliation: University of Toronto Country: Canada Publications
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Detail Information
Publications
In Vivo Uptake of β-Amyloid by Non-Plaque Associated MicrogliaCheryl A Hawkes
Centre for Research in Neurodegenerative Diseases, 6 Queen s Park Crescent West, Toronto, Ontario, M5S 3H2, Canada
Curr Alzheimer Res 9:890-901. 2012..These results reveal a novel, beneficial role for non-plaque associated microglia in the regulation of cerebral Aβ levels in a mouse model of AD...
Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer's diseaseAdrienne Dorr
Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario, Canada
Brain 135:3039-50. 2012....
Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface bindingDavid A Bateman
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
BMC Neurosci 8:29. 2007..Here we investigate the relationship between peptide aggregation and cell surface binding of three forms of Abeta (Abeta40, Abeta42, and an Abeta mutant)...- Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutantsPaul M Gorman
Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 2M9, Canada
BMC Neurosci 9:17. 2008..The transmembrane domain (TM) of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains... - Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse modelJoAnne McLaurin
Centre for Research in Neurodegenerative Diseases, 6 Queen s Park Crescent West, Toronto, Ontario M5S 3H2 Canada
Nat Med 12:801-8. 2006.... - Interactions of Alzheimer amyloid-beta peptides with glycosaminoglycans effects on fibril nucleation and growthJ McLaurin
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
Eur J Biochem 266:1101-10. 1999.... - Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesisJ McLaurin
Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Pharmacopsychiatry 36:S130-5. 2003..Our results suggest that the enhanced amyloidogenic properties of Abeta42 are not correlated with fibril formation but aggregation on bilayer surfaces... - Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesisJ McLaurin
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5S 3G9
Ann N Y Acad Sci 977:376-83. 2002..Our results suggest that the enhanced amyloidogenic properties of Abeta42 are not correlated with fibril formation, but with aggregation on bilayer surfaces... - Therapeutically effective antibodies against amyloid-beta peptide target amyloid-beta residues 4-10 and inhibit cytotoxicity and fibrillogenesisJ McLaurin
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
Nat Med 8:1263-9. 2002..These findings provide the basis for improved immunization antigens as well as attempts to design small-molecule mimics as alternative therapies... - A sulfated proteoglycan aggregation factor mediates amyloid-beta peptide fibril formation and neurotoxicityJ McLaurin
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
Amyloid 6:233-43. 1999..We also propose that the MAF model system may be useful in delineating these interactions and represent a means to develop and examine potential inhibitors of the proteoglycan effects... - Effect of amino-acid substitutions on Alzheimer's amyloid-beta peptide-glycosaminoglycan interactionsJ McLaurin
Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada
Eur J Biochem 267:6353-61. 2000.... - Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit abeta -induced toxicityJ McLaurin
Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine, University of Toronto, Toronto, Ontario, M5S 3H2, Canada
J Biol Chem 275:18495-502. 2000..Inositol stereoisomers are naturally occurring molecules that readily cross the blood-brain barrier and may represent a viable treatment for AD through the complexation of Abeta and attenuation of Abeta neurotoxic effects... - Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis and neurotoxicityC M Yip
Institute for Biomaterials and Biomedical Engineering and Centre for Studies in Molecular Imaging, University of Toronto, Ontario, Canada
J Mol Biol 311:723-34. 2001..These results collectively suggest that Abeta-cell surface interactions are mediated by cellular cholesterol levels, the distribution of cholesterol throughout the cell, and membrane fluidity... - Assembly of Alzheimer's amyloid-beta fibrils and approaches for therapeutic interventionD S Yang
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
Amyloid 8:10-9. 2001..In addition, the use of small compounds that interfere with the proteoglycan-amyloid pathway may be effective therapeutic agents that can be assessed through the use of these transgenic models... - Amyloid-beta peptide assembly: a critical step in fibrillogenesis and membrane disruptionC M Yip
Institute for Biomaterials and Biomedical Engineering and Centre for Studies in Molecular Imaging, University of Toronto, Toronto, Ontario M5S 3G9 Canada
Biophys J 80:1359-71. 2001..These observations suggest that the fibrillogenic properties of Abeta peptide are in part a consequence of membrane composition, peptide sequence, and mode of assembly within the membrane... - Examining the zinc binding site of the amyloid-beta peptideD S Yang
Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
Eur J Biochem 267:6692-8. 2000..Our results indicate that substitution of either His13 or His14 but not His6 eliminates the zinc-mediated effects. These observations indicate a specific zinc binding site within Abeta that involves these central histidine residues... - alpha-Synuclein membrane interactions and lipid specificityE Jo
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
J Biol Chem 275:34328-34. 2000..These results suggest that alpha-Syn membrane interactions are physiologically important and the lipid composition of the cellular membranes may affect these interactions in vivo... - A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's diseaseC Janus
Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Ontario, Canada
Nature 408:979-82. 2000..This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species... - Immunization with amyloid-beta using GM-CSF and IL-4 reduces amyloid burden and alters plaque morphologyKevin DaSilva
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
Neurobiol Dis 23:433-44. 2006..Thus, GM-CSF and IL-4 are effective adjuvants for Abeta immunotherapy... - Vaccine development for Alzheimer's diseaseKevin A DaSilva
Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen's Park Crescent West, Toronto, Ontario, Canada, M5S 3H2
Curr Pharm Des 12:4283-93. 2006..If so, Abeta vaccination could supplant current symptomatic treatment and represent one of the first therapeutic options for AD based on the amyloid cascade hypothesis... - Properties of scyllo-inositol as a therapeutic treatment of AD-like pathologyDaniela Fenili
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, M5S 3H2, Canada
J Mol Med (Berl) 85:603-11. 2007..These combined results demonstrate that scyllo-inositol accumulates within the CNS up to tenfold endogenous levels and does not interfere with phosphatidylinositol lipid production... - TgCRND8 amyloid precursor protein transgenic mice exhibit an altered gamma-secretase processing and an aggressive, additive amyloid pathology subject to immunotherapeutic modulationGregory D Van Vickle
The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, Arizona 85351, USA
Biochemistry 46:10317-27. 2007..However, given the phylogenetic distance and the differences in APP processing and Abeta chemistry between Tg mice and AD, caution should be applied in projecting mouse therapeutic interventions onto human subjects... - Immunotherapy as treatment for Alzheimer's diseaseCheryl A Hawkes
Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
Expert Rev Neurother 7:1535-48. 2007.... - Modulation of amyloid-beta aggregation and toxicity by inosose stereoisomersMark Nitz
Department of Chemistry, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ontario, Canada
FEBS J 275:1663-74. 2008..These molecules help in the further elucidation of the structure-activity relationships of inositol-Abeta interactions and identify both allo-inositol and epi-2-inosose as in vitro inhibitors of Abeta aggregation... - PPAR-alpha expression inversely correlates with inflammatory cytokines IL-1beta and TNF-alpha in aging ratsDavid S Gelinas
Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Tanz Neuroscience Building, 6 Queen s Park Crescent West, Toronto, Ontario, M5S3H2, Canada
Neurochem Res 30:1369-75. 2005..These findings underline a differential role for DHEAS in PPAR-alpha expression that is age-dependent, and also, that beneficial effects of DHEAS on cognitive function are unlikely mediated by a decrease in cytokine expression... - Identification and structural characterisation of carboxy-terminal polypeptides and antibody epitopes of Alzheimer's amyloid precursor protein using high-resolution mass spectrometryXiaodan Tian
Department of Chemistry, Analytical Chemistry, University of Konstanz, 78457 Konstanz, Germany
Eur J Mass Spectrom (Chichester, Eng) 11:547-56. 2005..These results demonstrate high-resolution FT-ICR-MS as a powerful method for characterising biochemical pathways and molecular recognition structures of APP... - Biophysical characterization of longer forms of amyloid beta peptides: possible contribution to flocculent plaque formationMark H L Lambermon
Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
J Neurochem 95:1667-76. 2005..All peptides accelerated the random to beta-structural transitions and fibril formation of Abeta40 and 42... - Phenotypic and functional changes in glial cells as a function of ageWai H Yu
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada
Neurobiol Aging 23:105-15. 2002..In particular, IL-1beta was increased 2 fold between adult and aged glial cells. The elevated cytokine expression may contribute to enhanced susceptibility to neurodegenerative diseases... - Abeta42-peptide assembly on lipid bilayersChristopher M Yip
Department of Chemical Engineering and Applied Chemistry, Institute for Biomaterials and Biomedical Engineering and Centre for Studies in Molecular Imaging, University of Toronto, Toronto, Ontario, Canada M5S 3G9
J Mol Biol 318:97-107. 2002..Our results demonstrate that the composition of the lipid bilayer governs the outcome of Abeta interactions... - Design of peptide-based inhibitors of human islet amyloid polypeptide fibrillogenesisLouise A Scrocchi
Centre for Research in Neurodegenerative Diseases, University of Toronto, Tanz Neuroscience Building, 6 Queen s Park Crescent West, Toronto, Ontario, Canada M5S 3H2
J Mol Biol 318:697-706. 2002..This study has identified internal IAPP peptide fragments which can regulate fibrillogenesis and may be of therapeutic use for the treatment of type-2 diabetes... - Current concepts and future prospects for Alzheimer disease vaccinesFrank L Heppner
Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
Alzheimer Dis Assoc Disord 18:38-43. 2004..Such knowledge might facilitate the design of specific vaccination regimens, allowing exclusive targeting of A beta plaques without inducing detrimental side effects... - alpha-Synuclein-synaptosomal membrane interactions: implications for fibrillogenesisEuijung Jo
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
Eur J Biochem 271:3180-9. 2004..These results suggest that alterations in alpha-synuclein-lipid interactions may contribute to physiological changes detected in early onset PD... - Immunotherapy for Alzheimer's diseaseDavid S Gelinas
Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen's Park Crescent West, Toronto, ON M5S 3H2, Canada
Proc Natl Acad Sci U S A 101:14657-62. 2004..In harnessing and steering the immune system, an effective response can be generated against A beta. If this proves successful, A beta vaccination could provide the first definitive treatment for AD... - Interaction of human and mouse Abeta peptidesJustin Fung
Centre for Research in Neurodegenerative Diseases, Ontario Cancer Institute, Toronto, Ontario, Canada
J Neurochem 91:1398-403. 2004..Furthermore, these results suggest that the presence of endogenous murine Abeta in human APP transgenic mice does not account for the increased solubility of plaques... - Ciglitazone increases basal cytokine expression in the central nervous system of adult ratsDavid S Gelinas
Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, 6 Queen s Park Crescent West, Toronto, Ontario, Canada M5S3H2
Brain Res 1034:139-46. 2005.... - Refining an Alzheimer's vaccine to avoid an inflammatory responseMary E Brown
Centre for Research in Neurodegenerative Diseases, University of Toronto, Tanz Neuroscience Building, 6 Queen's Park Crescent West, Toronto, Ontario, M5S 3H2, Canada
Expert Opin Biol Ther 5:809-16. 2005..In harnessing and steering the immune system, an effective response can be generated against Abeta, one that might have attenuated immune responses with robust disease-altering activity... - Cholesterol and apoe: a target for Alzheimer's disease therapeuticsDaniela Fenili
Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Curr Drug Targets CNS Neurol Disord 4:553-67. 2005..Elevated cholesterol levels and presence of the apolipoprotein E eta4 allele increase AD risk. How these two factors may contribute to AD pathogenesis and some therapeutic strategies for alleviating AD risk will be discussed... - Contribution of simple saccharides to the stabilization of amyloid structureJustin Fung
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ont, M5S 3H2, Canada
Biochem Biophys Res Commun 328:1067-72. 2005..Our studies suggest that utilization of a combinatorial strategy to alter H-bonding capacity across a simple carbohydrate molecule may represent a novel drug design strategy... - Genomic DNA functions as a universal external standard in quantitative real-time PCRJames J Yun
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
Nucleic Acids Res 34:e85. 2006..A simple method that can assist achieving absolute quantification of gene expression would broadly enhance the uses of real-time qPCR and in particular, augment the evaluation of global gene expression studies... - Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregationYedi Sun
Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ont, Canada M5S 3H6
Bioorg Med Chem 16:7177-84. 2008..The other derivatives showed some alterations in the morphology of the Abeta42 fibers produced. These findings indicate the importance of all of the hydroxyl groups of scyllo-inositol for complete inhibition of Abeta aggregation...