T E Golde

Summary

Affiliation: Mayo Clinic
Country: USA

Publications

  1. ncbi Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease
    T E Golde
    Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA
    Biochim Biophys Acta 1502:172-87. 2000
  2. ncbi Quantitative and mechanistic studies of Abeta immunotherapy
    Todd E Golde
    Mayo Clinic, College of Medicine, Department of Neuroscience, Mayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    CNS Neurol Disord Drug Targets 8:31-49. 2009
  3. pmc The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative disease
    Todd E Golde
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Mol Neurodegener 4:8. 2009
  4. pmc Alzheimer disease therapy: can the amyloid cascade be halted?
    Todd E Golde
    Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Clin Invest 111:11-8. 2003
  5. doi Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins
    Todd E Golde
    Department of Neuroscience, Mayo Clinic, College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, United States
    Semin Cell Dev Biol 20:225-30. 2009
  6. pmc Targeting Abeta and tau in Alzheimer's disease, an early interim report
    Todd E Golde
    Department of Neuroscience, College of Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    Exp Neurol 223:252-66. 2010
  7. ncbi The Abeta hypothesis: leading us to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease
    Todd E Golde
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Brain Pathol 15:84-7. 2005
  8. ncbi Filling the gaps in the abeta cascade hypothesis of Alzheimer's disease
    Todd E Golde
    Mayo Clinic College of Medicine, Department of Neuroscience, Mayo Clinic Jacksonville 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
    Curr Alzheimer Res 3:421-30. 2006
  9. ncbi Physiologic and pathologic events mediated by intramembranous and juxtamembranous proteolysis
    Todd E Golde
    Mayo Clinic Jacksonville, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Sci STKE 2003:RE4. 2003
  10. ncbi Disease modifying therapy for AD?
    Todd E Golde
    Mayo Clinic College of Medicine, Department of Neuroscience, Mayo Clinic Jacksonville 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    J Neurochem 99:689-707. 2006

Detail Information

Publications67

  1. ncbi Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease
    T E Golde
    Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA
    Biochim Biophys Acta 1502:172-87. 2000
    ..This review will highlight those aspects of Abeta biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study...
  2. ncbi Quantitative and mechanistic studies of Abeta immunotherapy
    Todd E Golde
    Mayo Clinic, College of Medicine, Department of Neuroscience, Mayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    CNS Neurol Disord Drug Targets 8:31-49. 2009
    ..We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Abeta Abs in AD and optimize antibody (Ab) mediated therapy for AD...
  3. pmc The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative disease
    Todd E Golde
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Mol Neurodegener 4:8. 2009
    ..Finally, we will need to develop novel therapies that interfere with these steps and demonstrate that such therapies alone, or in combination with therapies that target the trigger of these devastating diseases, have clinical benefit...
  4. pmc Alzheimer disease therapy: can the amyloid cascade be halted?
    Todd E Golde
    Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Clin Invest 111:11-8. 2003
  5. doi Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins
    Todd E Golde
    Department of Neuroscience, Mayo Clinic, College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, United States
    Semin Cell Dev Biol 20:225-30. 2009
    ..Further study of the SPP family is needed in order to understand their biological roles and their potential as therapeutic targets...
  6. pmc Targeting Abeta and tau in Alzheimer's disease, an early interim report
    Todd E Golde
    Department of Neuroscience, College of Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    Exp Neurol 223:252-66. 2010
    ..Finally, we will discuss the challenges for an appropriate "triage" after potential disease modifying therapies targeting tau and Abeta have entered clinical trials...
  7. ncbi The Abeta hypothesis: leading us to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease
    Todd E Golde
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Brain Pathol 15:84-7. 2005
    ..In this review, the evidence supporting the Abeta hypothesis and the recent advances in anti-Abeta therapy are discussed...
  8. ncbi Filling the gaps in the abeta cascade hypothesis of Alzheimer's disease
    Todd E Golde
    Mayo Clinic College of Medicine, Department of Neuroscience, Mayo Clinic Jacksonville 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
    Curr Alzheimer Res 3:421-30. 2006
    ....
  9. ncbi Physiologic and pathologic events mediated by intramembranous and juxtamembranous proteolysis
    Todd E Golde
    Mayo Clinic Jacksonville, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Sci STKE 2003:RE4. 2003
    ..Because some of the proteases mediating IP and JP can be selectivity inhibited, inhibitors targeting these proteases are likely to alter both physiologic and pathologic events triggered by IP and JP...
  10. ncbi Disease modifying therapy for AD?
    Todd E Golde
    Mayo Clinic College of Medicine, Department of Neuroscience, Mayo Clinic Jacksonville 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    J Neurochem 99:689-707. 2006
    ..This review will highlight both the promise of and the obstacles to developing such disease modifying AD therapies...
  11. ncbi Presenilins as therapeutic targets for the treatment of Alzheimer's disease
    T E Golde
    Mayo Clinic Jacksonville, Dept of Neuroscience, 4500 San Pablo Road, 32224, Jacksonville, FL, USA
    Trends Mol Med 7:264-9. 2001
    ....
  12. ncbi Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition
    P Das
    Department of Neurosciences, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Neurobiol Aging 22:721-7. 2001
    ..These results indicate that in Tg2576 mice, Abeta1-42 immunization is more effective at preventing additional Abeta accumulation and does not result in significant clearance of pre-existing Abeta deposits...
  13. ncbi Reduction of Abeta accumulation in the Tg2576 animal model of Alzheimer's disease after oral administration of the phosphatidyl-inositol kinase inhibitor wortmannin
    S J Haugabook
    Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    FASEB J 15:16-18. 2001
    ....
  14. pmc NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo
    Jason L Eriksen
    Department of Neuroscience, Mayo Graduate School, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Clin Invest 112:440-9. 2003
    ..Because R-flurbiprofen reduces Abeta42 levels by targeting gamma-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Abeta42 lowering agent...
  15. ncbi Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides
    P A Lewis
    Department of Neuroscience and Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Biochim Biophys Acta 1537:58-62. 2001
    ..Significantly, expression of Abeta42 from the BRI-Abeta42 construct resulted in no increase in secreted Abeta40, suggesting that the majority of Abeta42 is not trimmed by carboxypeptidase to Abeta40 in the secretory pathway...
  16. ncbi Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice
    Yona Levites
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    J Neurosci 26:11923-8. 2006
    ..As opposed to transgenic approaches, these studies also establish a "somatic brain transgenic" paradigm to rapidly and cost-effectively evaluate potential modifiers of AD-like pathology in AD mouse models...
  17. ncbi High throughput screens for the identification of compounds that alter the accumulation of the Alzheimer's amyloid beta peptide (Abeta)
    S J Haugabook
    Mayo Clinic Jacksonville, Birdsall Building Room 253, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    J Neurosci Methods 108:171-9. 2001
    ..If compounds such as these can be identified that lower Abeta in the brain, they may represent one of the fastest and most cost effective methods to therapy...
  18. ncbi Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor
    Andrew C Nyborg
    Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Biol Chem 279:15153-60. 2004
    ..Collectively these data suggest that SPP exists in vivo as a functional dimer...
  19. ncbi Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-/- knock-out mice
    Pritam Das
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
    J Neurosci 23:8532-8. 2003
    ..We conclude that after Abeta immunization, the effects of anti-Abeta antibodies on Abeta deposition in APP Tg2576 transgenic mice are not dependent on FcR-mediated phagocytic events...
  20. pmc Possible mechanisms of action of NSAIDs and related compounds that modulate gamma-secretase cleavage
    Thomas Kukar
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Curr Top Med Chem 8:47-53. 2008
    ..The evidence indicating that these chemicals modulate the production of Abeta peptides by directly interacting with the gamma-secretase complex is summarized...
  21. pmc Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice
    Thomas Kukar
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    BMC Neurosci 8:54. 2007
    ..In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Abeta loads in Tg2576 APP mice...
  22. pmc Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model
    Yona Levites
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    J Clin Invest 116:193-201. 2006
    ..These data suggest that selective targeting of Abeta42 or Abeta40 may be an effective strategy to prevent amyloid deposition, but may have limited benefit in a therapeutic setting...
  23. pmc BRI2 (ITM2b) inhibits Abeta deposition in vivo
    Jungsu Kim
    Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Neurosci 28:6030-6. 2008
    ..These studies demonstrate that BRI2 is a novel mediator of Abeta deposition in vivo...
  24. ncbi Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production
    Thomas Kukar
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Nat Med 11:545-50. 2005
    ....
  25. ncbi Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains
    Suzanne Wahrle
    Department of Neuroscience and Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Neurobiol Dis 9:11-23. 2002
    ..Thus, altering cholesterol levels may influence the development of Alzheimer's disease (AD) by influencing production and deposition of Abeta within cholesterol rich membrane microdomains...
  26. pmc Substrate-targeting gamma-secretase modulators
    Thomas L Kukar
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Nature 453:925-9. 2008
    ..These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets...
  27. ncbi Open peer commentary regarding Abeta immunization and CNS inflammation by Pasinetti et al
    Pritam Das
    Laboratory of Molecular Neurobiology, Department of Neuroscience, Mayo Clinic, Birdsall 327, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurobiol Aging 23:671-4; discussion 683-4. 2002
  28. ncbi The presenilin 1 C92S mutation increases abeta 42 production
    P A Lewis
    Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Biochem Biophys Res Commun 277:261-3. 2000
    ..elegans into a context whereby its effect on mammalian cells can be evaluated suggests that all FAD-linked PS1 mutants result in increased Abeta42 production through a partial loss of function mechanism...
  29. pmc Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition
    Paramita Chakrabarty
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    FASEB J 24:548-59. 2010
    ..This is the first study that methodically dissects the contribution of mIL-6 with regard to its potential role in modulating Abeta deposition in vivo...
  30. pmc IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice
    Paramita Chakrabarty
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    J Immunol 184:5333-43. 2010
    ....
  31. ncbi Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase
    Andrew C Nyborg
    Department of Neuroscience, Mayo Clinic Jacksonville, Mayo Clinic College of Medicine, 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
    FASEB J 20:1671-9. 2006
    ..Based on these data, we hypothesize that mSPP is a potential a novel therapeutic target for malaria...
  32. ncbi Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models
    Yona Levites
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    FASEB J 20:2576-8. 2006
    ..Such quantitative data suggest that the mAbs are either indirectly enhancing clearance of Abeta or targeting a low abundance aggregation intermediate...
  33. ncbi FAD-linked mutations in presenilin 1 alter the length of Abeta peptides derived from betaAPP transmembrane domain mutants
    M Paul Murphy
    Department of Neuroscience, Laboratory of Molecular Neurobiology, Mayo Clinic Jacksonville, FL, USA
    Biochim Biophys Acta 1586:199-209. 2002
    ..These results support a model in which the FAD-linked mutants subtly alter the conformation of the gamma-secretase complex to favor the production of long Abeta...
  34. ncbi Immune responses against Abeta1-42 in HLA class II transgenic mice: implications for Abeta1-42 immune-mediated therapies
    Pritam Das
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurobiol Aging 24:969-76. 2003
    ..These studies in mice suggest that the presence of certain MHC class II molecules or combinations of class II molecules can potentially influence the overall immune response against Abeta1-42...
  35. ncbi Peptide-based, irreversible inhibitors of gamma-secretase activity
    Siân C Piper
    Mayo Clinic Jacksonville, Birdsall Medical Research Building, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Biochem Biophys Res Commun 305:529-33. 2003
    ..Since such inhibitors have been shown to bind catalytic residues in other aspartyl proteases (e.g., HIV protease), they might be used to determine if the transmembrane aspartates of PSs are involved directly in substrate cleavage...
  36. ncbi A signal peptide peptidase (SPP) reporter activity assay based on the cleavage of type II membrane protein substrates provides further evidence for an inverted orientation of the SPP active site relative to presenilin
    Andrew C Nyborg
    Mayo Clinic, Mayo Clinic College of Medicine, Department of Neuroscience, Jacksonville, Florida 32224, USA
    J Biol Chem 279:43148-56. 2004
    ..This assay should prove useful for additional functional studies of SPP as well as evaluation of SPP and gamma-secretase inhibitors...
  37. ncbi A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch
    Zareen Amtul
    Department of Neuroscience and Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Neurobiol Dis 9:269-73. 2002
    ..The distinct clinical phenotype associated with this mutation suggests that chronic partial inhibition of gamma-secretase activity may result in neurodegeneration...
  38. pmc Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins
    Ronald L Klein
    Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
    Mol Ther 13:517-27. 2006
    ..While the toxicity observed with GFP expression warrants great caution, the efficient AAV8 is promising for animal models of neurodegenerative diseases and potentially as well for gene therapy of brain diseases...
  39. ncbi Homing in on intracellular Abeta?
    Todd E Golde
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Neuron 45:639-42. 2005
    ..link appearance of intraneuronal Abeta to cognitive impairments and then show that "clearance" of intraneuronal Abeta by anti-Abeta antibodies restores cognitive deficits...
  40. ncbi Overexpression of nicastrin increases Abeta production
    M Paul Murphy
    Mayo Clinic Jacksonville, Laboratory of Molecular Neurobiology, Department of Neuroscience, 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
    FASEB J 17:1138-40. 2003
    ....
  41. pmc Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity
    Yong Jie Zhang
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Proc Natl Acad Sci U S A 106:7607-12. 2009
    ..Finally, by generating a conformation-dependent antibody that detects C-terminal fragments, we show that this toxic cleavage product is specific for pathologic inclusions in human TDP-43 proteinopathies...
  42. ncbi The pathogenesis of Alzheimer's disease and the role of Abeta42
    Todd E Golde
    CNS Spectr 12:4-6. 2007
  43. doi Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase
    Eva Czirr
    Molecular Neuropathology Group, Department of Neuropathology, Heinrich Heine University, D 40225 Duesseldorf, Germany
    J Biol Chem 283:17049-54. 2008
    ..These data provide evidence that Abeta42 and Abeta38 species can be independently generated by gamma-secretase and argue against a precursor-product relationship between these peptides...
  44. ncbi Statins reduce amyloid-beta production through inhibition of protein isoprenylation
    Stephen M Ostrowski
    Department of Neurosciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    J Biol Chem 282:26832-44. 2007
    ..These studies provide insight into the mechanisms by which statins may reduce AD pathogenesis...
  45. ncbi Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals
    Douglas R Galasko
    Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
    Alzheimer Dis Assoc Disord 21:292-9. 2007
    ..The safety, tolerability, and pharmacokinetic profile of R-flurbiprofen in these older individuals support the ongoing studies of this compound in patients with Alzheimer disease...
  46. ncbi Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs
    Bruno Martoglio
    Institute of Biochemistry, Swiss Federal Institute of Technology ETH, Zurich, Switzerland
    Hum Mol Genet 12:R201-6. 2003
    ..Herein, we will review the recent advances in our understanding of the PS/SPP family of proteases as well as discuss aspects of intramembrane cleavage that are not well understood...
  47. ncbi Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity
    Sascha Weggen
    Department of Neurosciences, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 278:31831-7. 2003
    ..In sum, these results strongly suggest that NSAIDs represent a founding group of compounds that lower A beta 42 production by direct modulation of gamma-secretase activity or its substrate...
  48. ncbi Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain
    Sascha Weggen
    Department of Neurosciences, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 278:30748-54. 2003
    ....
  49. ncbi Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction
    Salvatore Oddo
    Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
    Neuron 39:409-21. 2003
    ....
  50. ncbi Inflammation takes on Alzheimer disease
    Todd E Golde
    Nat Med 8:936-8. 2002
  51. ncbi TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells
    Tanapat Palaga
    Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA
    J Immunol 171:3019-24. 2003
    ..Our data reveal a new, nondevelopmental function of Notch as a previously unknown key link in peripheral T cell activation and cytokine secretion...
  52. ncbi Bringing amyloid into focus
    Todd E Golde
    Nat Biotechnol 23:552-4. 2005
  53. pmc Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle
    Michael C Sugarman
    Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 99:6334-9. 2002
    ..These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM...
  54. ncbi Inhibitors of Rho-kinase modulate amyloid-beta (Abeta) secretion but lack selectivity for Abeta42
    Stefanie Leuchtenberger
    Emmy Noether Research Group, Institute of Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg University Mainz, Mainz, Germany
    J Neurochem 96:355-65. 2006
    ..Taken together, these results seem to exclude a mechanistic involvement of ROCK in the Abeta42-lowering activity of NSAIDs...
  55. ncbi C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation
    Jun Wang
    Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 96:218-27. 2006
    ..Together, these observations strongly support the hypothesis that the PAL motif contributes to the active site conformation of gamma-secretase and of SPP...
  56. ncbi Detection of presenilin-1 homodimer formation in intact cells using fluorescent lifetime imaging microscopy
    Lauren Herl
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 340:668-74. 2006
    ..Taken together these data suggest that PS1 dimerization occurs during normal PS1 function...
  57. ncbi Inclusion-body myositis and Alzheimer disease: two sides of the same coin, or different currencies altogether?
    M Paul Murphy
    Department of Molecular and Cellular Biochemistry, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
    Neurology 66:S65-8. 2006
  58. ncbi The non-cyclooxygenase targets of non-steroidal anti-inflammatory drugs, lipoxygenases, peroxisome proliferator-activated receptor, inhibitor of kappa B kinase, and NF kappa B, do not reduce amyloid beta 42 production
    Sarah A Sagi
    Department of Neurosciences, University of California San Diego, La Jolla, California 921093, USA
    J Biol Chem 278:31825-30. 2003
    ..Thus, NSAIDs do not appear to alter A beta 42 production indirectly through previously identified cellular targets and may interact directly with the gamma-secretase complex itself to affect amyloid production...
  59. pmc A physiologic signaling role for the gamma -secretase-derived intracellular fragment of APP
    Malcolm A Leissring
    Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 99:4697-702. 2002
    ....
  60. ncbi Identification of a novel family of presenilin homologues
    Chris P Ponting
    MRC Functional Genetics Unit, University of Oxford, Department of Human Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK
    Hum Mol Genet 11:1037-44. 2002
    ..Based on these findings, we propose that PSs and PSHs represent different sub-branches of a larger family of polytopic membrane-associated aspartyl proteases...
  61. pmc Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells
    Jeremy B Samon
    Program in Animal Biotechnology and Biomedical Science, University of Massachusetts Amherst, MA 01003, USA
    Blood 112:1813-21. 2008
    ..Together, these findings indicate that the Notch and TGFbeta signaling pathways cooperatively regulate Foxp3 expression and regulatory T-cell maintenance both in vitro and in vivo...
  62. ncbi Signal peptide peptidase: biochemical properties and modulation by nonsteroidal antiinflammatory drugs
    Toru Sato
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 45:8649-56. 2006
    ..Together, these findings suggest that SPP and presenilin share certain biochemical properties, including a conserved drug-binding site for allosteric modulation of substrate proteolysis...
  63. ncbi Presenilin regulates capacitative calcium entry dependently and independently of gamma-secretase activity
    Yama Akbari
    Department of Neurobiology and Behavior, University of California, Irvine, CA 92697 4545, USA
    Biochem Biophys Res Commun 322:1145-52. 2004
    ..These data suggest that changes in the structural components of presenilin can modulate CCE independent of its function in gamma-secretase activity and intracellular calcium stores...
  64. ncbi Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells
    Christine L Curry
    Department of Pathology and Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153 5385, USA
    Oncogene 24:6333-44. 2005
    ..The results indicate that KS cells overexpress activated Notch and interruption of Notch signaling inhibits KS cell growth. Thus, targeting Notch signaling may be of therapeutic value in KS patients...
  65. ncbi Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21
    Lisa M Minter
    Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 01003, USA
    Nat Immunol 6:680-8. 2005
    ..Thus, using gamma-secretase inhibitors to modulate Notch signaling may prove beneficial in treating TH1-mediated autoimmunity...
  66. ncbi Notch inhibition in Kaposi's sarcoma tumor cells leads to mitotic catastrophe through nuclear factor-kappaB signaling
    Christine L Curry
    Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA
    Mol Cancer Ther 6:1983-92. 2007
    ..Taken together, these studies suggest that Notch inhibition can initiate aberrant mitosis by inducing NF-kappaB activity that inappropriately increases cyclin B1 resulting in cell death via mitotic catastrophe...