Paul Mathews

Summary

Affiliation: Nathan Kline Institute
Country: USA

Publications

  1. ncbi Effect of anti-inflammatory agents on transforming growth factor beta over-expressing mouse brains: a model revised
    Pierre Lacombe
    Laboratoire de Recherches C r brovasculaires, CNRS FRE 2363, Paris, France
    J Neuroinflammation 1:11. 2004
  2. ncbi Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease
    P M Mathews
    Nathan Kline Institute, New York University School of Medicine, Organgeburg, New York 10962, USA
    Mol Med 6:878-91. 2000
  3. ncbi Calpain activity regulates the cell surface distribution of amyloid precursor protein. Inhibition of calpains enhances endosomal generation of beta-cleaved C-terminal APP fragments
    Paul M Mathews
    Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Biol Chem 277:36415-24. 2002
  4. ncbi The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review
    R A Nixon
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    Neurochem Res 25:1161-72. 2000
  5. ncbi Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis
    Martin C Herzig
    Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, , , Germany
    Nat Neurosci 7:954-60. 2004
  6. ncbi Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation
    Magdalena Sastre
    Departments of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA
    Neurobiol Aging 25:1033-43. 2004
  7. ncbi Functional domains in presenilin 1: the Tyr-288 residue controls gamma-secretase activity and endoproteolysis
    Hanna Laudon
    Department of Neurotec, Division of Experimental Geriatrics, Karolinska Institutet, Novum, SE 141 86 Huddinge, Sweden
    J Biol Chem 279:23925-32. 2004
  8. ncbi Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins
    Veronique Dorval
    Department of Medical Biophysics and Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada, M5S 3HZ
    Biochem J 404:309-16. 2007
  9. ncbi Alzheimer's presenilin 1 modulates sorting of APP and its carboxyl-terminal fragments in cerebral neurons in vivo
    Sam Gandy
    Farber Institute for Neurosciences and the Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    J Neurochem 102:619-26. 2007
  10. ncbi Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo
    Mark Burns
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 23:5645-9. 2003

Research Grants

  1. Cell-based screens for Alzheimer's disease therapeutics
    Paul Mathews; Fiscal Year: 2004
  2. Calpain Regulation of Amyloid-beta and Plaque Formation
    Paul Mathews; Fiscal Year: 2007

Collaborators

Detail Information

Publications32

  1. ncbi Effect of anti-inflammatory agents on transforming growth factor beta over-expressing mouse brains: a model revised
    Pierre Lacombe
    Laboratoire de Recherches C r brovasculaires, CNRS FRE 2363, Paris, France
    J Neuroinflammation 1:11. 2004
    ..Identification of the thioflavin-S-positive material will facilitate the full appraisal of the clinical implication of the effects of anti-inflammatory drugs, and provide a more thorough understanding of TGF-beta1 actions in brain...
  2. ncbi Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease
    P M Mathews
    Nathan Kline Institute, New York University School of Medicine, Organgeburg, New York 10962, USA
    Mol Med 6:878-91. 2000
    ..Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD)...
  3. ncbi Calpain activity regulates the cell surface distribution of amyloid precursor protein. Inhibition of calpains enhances endosomal generation of beta-cleaved C-terminal APP fragments
    Paul M Mathews
    Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Biol Chem 277:36415-24. 2002
    ....
  4. ncbi The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review
    R A Nixon
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    Neurochem Res 25:1161-72. 2000
    ..These and other studies support the view that the progressive alterations of lysosomal function observed during aging and Alzheimer's disease contribute importantly to the neurodegenerative process in Alzheimer's disease...
  5. ncbi Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis
    Martin C Herzig
    Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, , , Germany
    Nat Neurosci 7:954-60. 2004
    ....
  6. ncbi Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation
    Magdalena Sastre
    Departments of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA
    Neurobiol Aging 25:1033-43. 2004
    ..Notably, cystatin C association with Abeta results in a concentration-dependent inhibition of Abeta fibril formation...
  7. ncbi Functional domains in presenilin 1: the Tyr-288 residue controls gamma-secretase activity and endoproteolysis
    Hanna Laudon
    Department of Neurotec, Division of Experimental Geriatrics, Karolinska Institutet, Novum, SE 141 86 Huddinge, Sweden
    J Biol Chem 279:23925-32. 2004
    ..Thus, mutations at Tyr-288 do not affect gamma-secretase complex assembly but can differentially control endoproteolysis and gamma-secretase activity...
  8. ncbi Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins
    Veronique Dorval
    Department of Medical Biophysics and Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada, M5S 3HZ
    Biochem J 404:309-16. 2007
    ....
  9. ncbi Alzheimer's presenilin 1 modulates sorting of APP and its carboxyl-terminal fragments in cerebral neurons in vivo
    Sam Gandy
    Farber Institute for Neurosciences and the Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    J Neurochem 102:619-26. 2007
    ..The chimera experiment suggests that TGN-enrichment of a beta-/gamma-secretase substrate may play an integral role in the action of mutant PS1 to elevate brain levels of Abeta42...
  10. ncbi Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo
    Mark Burns
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 23:5645-9. 2003
    ..Our results show that aberrant cholesterol trafficking is associated with the potentiation of APP processing components in vivo, leading to an overall increase in Abeta levels...
  11. ncbi Rab5-stimulated up-regulation of the endocytic pathway increases intracellular beta-cleaved amyloid precursor protein carboxyl-terminal fragment levels and Abeta production
    Olivera M Grbovic
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Biol Chem 278:31261-8. 2003
    ..Our findings in this model system suggest that the endosomal pathology seen at the earliest stage of sporadic AD may contribute to APP proteolysis along a beta-amyloidogenic pathway...
  12. ncbi The in vivo brain interactome of the amyloid precursor protein
    Yu Bai
    Centre for Research in Neurodegenerative Diseases and Departments of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
    Mol Cell Proteomics 7:15-34. 2008
    ....
  13. ncbi Alzheimer's disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Abeta secretion: role for altered lysosomal hydrolase distribution in beta-amyloidogenesis
    Paul M Mathews
    Nathan Kline Institute and New York University School of Medicine, Orangeburg, New York 10962, USA
    J Biol Chem 277:5299-307. 2002
    ....
  14. ncbi Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease
    W Haung Yu
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    J Cell Biol 171:87-98. 2005
    ..Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD...
  15. ncbi Targeting the role of the endosome in the pathophysiology of Alzheimer's disease: a strategy for treatment
    Barbara A Tate
    CNS Discovery, Global Research and Development, Pfizer Inc, Groton, CT 06234, USA
    Sci Aging Knowledge Environ 2006:re2. 2006
    ..We present here the view that knowledge of the endosomal system in the disease can guide drug discovery of AD therapeutic agents...
  16. ncbi Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
    Rebecca Radde
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, Otfried Muller Strasse 27, D 72076 Tubingen, Germany
    EMBO Rep 7:940-6. 2006
    ....
  17. ncbi Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects
    Anne M Cataldo
    Laboratory for Molecular Neuropathology, Mailman Research Center, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA
    Am J Pathol 173:370-84. 2008
    ....
  18. ncbi Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models
    Weiqian Mi
    Nathan S Kline Institute, Orangeburg, New York 10962, USA
    Nat Genet 39:1440-2. 2007
    ..Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease...
  19. ncbi Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host
    Melanie Meyer-Luehmann
    Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, , , Germany
    Science 313:1781-4. 2006
    ..The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains...
  20. ncbi ELISA method for measurement of amyloid-beta levels
    Stephen D Schmidt
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA
    Methods Mol Biol 299:279-97. 2005
    ..Here we describe methods for the recovery of both soluble and deposited Abeta from brain tissue and the subsequent quantitation of the peptide by sandwich ELISA...
  21. ncbi Tissue processing prior to protein analysis and amyloid-beta quantitation
    Stephen D Schmidt
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA
    Methods Mol Biol 299:267-78. 2005
    ..The ELISA technique is described in detail in the following chapter...
  22. ncbi Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases
    Peter Mastrangelo
    Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 3H2
    Proc Natl Acad Sci U S A 102:8972-7. 2005
    ..Instead, our studies define functionally distinct gamma-secretase variants. We speculate that extrinsic components, in combination with core complexes, may tailor functional variants of this enzyme to their preferred substrates...
  23. ncbi Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins
    Dun Sheng Yang
    Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 277:28135-42. 2002
    ....
  24. ncbi Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype
    Richard Rozmahel
    Center for Research in Neurodegenerative Diseases, Department of Pharmacology, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 99:14452-7. 2002
    ..The dissociation of Notch S3-site and APP gamma-site cleavage activities will facilitate development of gamma-secretase inhibitors for treatment of Alzheimer's disease...
  25. ncbi Extracellular amyloid formation and associated pathology in neural grafts
    Melanie Meyer-Luehmann
    Department of Neuropathology, Institute of Pathology, University of Basel, , CH-4003 Basel, Switzerland
    Nat Neurosci 6:370-7. 2003
    ..Our results indicate that diffusion of soluble Abeta in the extracellular space is involved in the spread of Abeta pathology, and that extracellular amyloid formation can lead to neurodegeneration...
  26. ncbi In vivo reduction of amyloid-beta by a mutant copper transporter
    Amie L Phinney
    Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2
    Proc Natl Acad Sci U S A 100:14193-8. 2003
    ..These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide...
  27. ncbi Overexpression of human cystatin C in transgenic mice does not affect levels of endogenous brain amyloid Beta Peptide
    Monika Pawlik
    Department of Pharmacology, New York University School of Medicine, New York, NY, 10016, USA
    J Mol Neurosci 22:13-8. 2004
    ..Thus, in vivo overexpression of human cystatin C does not affect Abeta levels in mice that do not deposit Abeta...
  28. ncbi Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice
    Fabrizio Trinchese
    Department of Psychiatry, New York University School of Medicine, New York, NY, USA
    Ann Neurol 55:801-14. 2004
    ..In contrast, progression of LTP impairment correlated with the deterioration of working memory, suggesting that percentage of potentiation might be an indicator of the cognitive decline and disease progression in the APP/PS1 mice...
  29. ncbi Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes
    Hiroshi Hasegawa
    Centre for Research in Neurodegenerative Diseases, University of Toronto, West Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 279:46455-63. 2004
    ....
  30. ncbi Presenilin mutations in familial Alzheimer disease and transgenic mouse models accelerate neuronal lysosomal pathology
    Anne M Cataldo
    Laboratory for Molecular Neuropathology, Mailman Research Center, McLean Hospital, Belmont, Massachusetts, USA
    J Neuropathol Exp Neurol 63:821-30. 2004
    ..Our findings suggest that presenilin mutations have amyloid-independent effects on the lysosomal system, which are synergistic with the lysosomal system pathology that is associated with beta-amyloid...
  31. ncbi A synthetic peptide blocking the apolipoprotein E/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice
    Marcin Sadowski
    Department of Neurology, New York University School of Medicine, New York, New York, USA
    Am J Pathol 165:937-48. 2004
    ..Our experiments demonstrate that compounds blocking the interaction between Abeta and its pathological chaperones may be beneficial for treatment of beta-amyloid deposition in AD...
  32. ncbi Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease
    Fabrizio Trinchese
    Department of Pathology and Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University, New York, New York, USA
    J Clin Invest 118:2796-807. 2008
    ..Thus, calpain inhibition may prove useful in the alleviation of memory loss in AD...

Research Grants5

  1. Cell-based screens for Alzheimer's disease therapeutics
    Paul Mathews; Fiscal Year: 2004
    ..Additionally, once a compound is identified as effective in a cell-based system it has a much greater probability of in vivo efficacy than a compound identified, for example, using a purified enzyme screen. ..
  2. Calpain Regulation of Amyloid-beta and Plaque Formation
    Paul Mathews; Fiscal Year: 2007
    ....