Oksana Berezovska

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. pmc Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio
    Kengo Uemura
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    PLoS ONE 4:e7893. 2009
  2. ncbi request reprint Amyloid precursor protein associates with a nicastrin-dependent docking site on the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence lifetime imaging
    Oksana Berezovska
    Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 23:4560-6. 2003
  3. ncbi request reprint Monitoring proteins in intact cells
    Oksana Berezovska
    Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Sci Aging Knowledge Environ 2003:PE14. 2003
  4. pmc Reciprocal relationship between APP positioning relative to the membrane and PS1 conformation
    Kengo Uemura
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Mol Neurodegener 6:15. 2011
  5. ncbi request reprint Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein
    Oksana Berezovska
    Alzheimer Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurosci 25:3009-17. 2005
  6. ncbi request reprint Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation
    Alberto Lleo
    Alzheimer Research Unit, Massachusetts General Hospital, 114 16th St, Charlestown, Massachusetts 02129, USA
    Nat Med 10:1065-6. 2004
  7. ncbi request reprint Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion
    Mikko Hiltunen
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Biol Chem 281:32240-53. 2006
  8. pmc Mutations in amyloid precursor protein affect its interactions with presenilin/gamma-secretase
    Lauren Herl
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative, Diseases, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Mol Cell Neurosci 41:166-74. 2009
  9. ncbi request reprint Notch1 competes with the amyloid precursor protein for gamma-secretase and down-regulates presenilin-1 gene expression
    Alberto Lleo
    Alzheimer Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02114, USA
    J Biol Chem 278:47370-5. 2003
  10. ncbi request reprint Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader
    Anne V Thomas
    Alzheimer s Disease Research Laboratory, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 281:26400-7. 2006

Collaborators

Detail Information

Publications29

  1. pmc Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio
    Kengo Uemura
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    PLoS ONE 4:e7893. 2009
    ..Many modulators of gamma-secretase function have been described. We hypothesize that these modulators act by a common mechanism by allosterically modifying the structure of presenilin...
  2. ncbi request reprint Amyloid precursor protein associates with a nicastrin-dependent docking site on the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence lifetime imaging
    Oksana Berezovska
    Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 23:4560-6. 2003
    ..We interpret these results to suggest that there is a noncatalytic docking site closely associated with PS1-gamma-secretase...
  3. ncbi request reprint Monitoring proteins in intact cells
    Oksana Berezovska
    Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Sci Aging Knowledge Environ 2003:PE14. 2003
    ..This approach may have widespread applicability in studies of neurodegenerative disease mechanisms...
  4. pmc Reciprocal relationship between APP positioning relative to the membrane and PS1 conformation
    Kengo Uemura
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Mol Neurodegener 6:15. 2011
    ..abstract:..
  5. ncbi request reprint Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein
    Oksana Berezovska
    Alzheimer Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurosci 25:3009-17. 2005
    ..We propose that the conformational change we observed may therefore provide a shared molecular mechanism for FAD pathogenesis caused by a wide range of PS1 mutations...
  6. ncbi request reprint Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation
    Alberto Lleo
    Alzheimer Research Unit, Massachusetts General Hospital, 114 16th St, Charlestown, Massachusetts 02129, USA
    Nat Med 10:1065-6. 2004
    ....
  7. ncbi request reprint Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion
    Mikko Hiltunen
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Biol Chem 281:32240-53. 2006
    ..These findings suggest that changes in UBQLN1 steady-state levels affect APP trafficking and processing, thereby influencing the generation of Abeta...
  8. pmc Mutations in amyloid precursor protein affect its interactions with presenilin/gamma-secretase
    Lauren Herl
    Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative, Diseases, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Mol Cell Neurosci 41:166-74. 2009
    ..Mutant APP affects both intracellular location and efficiency of APP-PS1 interactions, thereby changing the Abeta(42/40) ratio...
  9. ncbi request reprint Notch1 competes with the amyloid precursor protein for gamma-secretase and down-regulates presenilin-1 gene expression
    Alberto Lleo
    Alzheimer Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02114, USA
    J Biol Chem 278:47370-5. 2003
    ..This finding suggests that Notch activation directly engages gamma-secretase and subsequently leads to diminished PS1 expression, suggesting a complex set of feedback interactions following Notch activation...
  10. ncbi request reprint Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader
    Anne V Thomas
    Alzheimer s Disease Research Laboratory, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 281:26400-7. 2006
    ....
  11. ncbi request reprint Activated Notch1 associates with a presenilin-1/gamma-secretase docking site
    Pavan Ramdya
    Alzheimer s Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurochem 87:843-50. 2003
    ..These results suggest a novel mechanism of ligand binding-mediated signal transduction of Notch1...
  12. ncbi request reprint Apolipoprotein E modulates gamma-secretase cleavage of the amyloid precursor protein
    Michael C Irizarry
    Alzheimer Disease Research Unit, Massachusetts General Hospital East, Charlestown, Massachusetts, USA
    J Neurochem 90:1132-43. 2004
    ..The apoE modulation of Abeta production and APP signaling is a potential mechanism affecting Alzheimer disease risk...
  13. ncbi request reprint Low density lipoprotein receptor-related protein (LRP) interacts with presenilin 1 and is a competitive substrate of the amyloid precursor protein (APP) for gamma-secretase
    Alberto Lleo
    Alzheimer Research Unit, Massachusetts Institute for Neurodegenerative Disorders, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:27303-9. 2005
    ..In conclusion, LRP is a PS1 interactor and can compete with APP for gamma-secretase enzymatic activity...
  14. pmc Neuronal activity and secreted amyloid β lead to altered amyloid β precursor protein and presenilin 1 interactions
    Xuejing Li
    Neurobiology of Alzheimer s Disease Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Neurobiol Dis 50:127-34. 2013
    ..Thus, under normal physiological conditions Aβ may impact its own production by modifying γ-secretase cleavage of APP. Disruption of this negative modulation may cause Aβ overproduction leading to neurotoxicity...
  15. pmc Distinct dendritic spine and nuclear phases of calcineurin activation after exposure to amyloid-β revealed by a novel fluorescence resonance energy transfer assay
    Hai Yan Wu
    Department of Neurology Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurosci 32:5298-309. 2012
    ..These results provide a framework for understanding the role of calcineurin in synaptic alterations associated with AD pathogenesis...
  16. ncbi request reprint 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...
  17. ncbi request reprint APP substitutions V715F and L720P alter PS1 conformation and differentially affect Abeta and AICD generation
    Giuseppina Tesco
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    J Neurochem 95:446-56. 2005
    ..In conclusion, both APPV715F and APPL720P change PS1 conformation with differential effects on Abeta and AICD production...
  18. pmc CHIP targets toxic alpha-Synuclein oligomers for degradation
    Julie E Tetzlaff
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Biol Chem 283:17962-8. 2008
    ....
  19. pmc Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer's disease
    Lara Wahlster
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease MIND, Massachusetts General Hospital, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA
    Acta Neuropathol 125:187-99. 2013
    ....
  20. ncbi request reprint Clinical, pathological, and biochemical spectrum of Alzheimer disease associated with PS-1 mutations
    Alberto Lleo
    Massachusetts General Hospital, Alzheimer Research Unit, Charleston, MA 02129, USA
    Am J Geriatr Psychiatry 12:146-56. 2004
    ..This represents a valuable model for identifying such factors and has potential implications for the development of new therapeutic strategies for delaying disease onset...
  21. ncbi request reprint Time-domain fluorescent plate reader for cell based protein-protein interaction and protein conformation assays
    Phill B Jones
    Athinoula A Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA
    J Biomed Opt 11:054024. 2006
    ..Presenilin 1 (PS1) is known to be important in Amyloid Precursor Protein (APP) processing in Alzheimer's disease. Using transfected cells, we demonstrate APP-PS1 interactions by FRET in a cell-based, 96-well plate format...
  22. doi request reprint Two postprocessing techniques for the elimination of background autofluorescence for fluorescence lifetime imaging microscopy
    Phillip B Jones
    Harvard Medical School, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disorders, 114 16th Street, Charlestown, Massachusetts 02129, USA
    J Biomed Opt 13:014008. 2008
    ....
  23. ncbi request reprint Designed helical peptides inhibit an intramembrane protease
    Chittaranjan Das
    Center for Neurologic Diseases, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 125:11794-5. 2003
    ..These findings are consistent with helical peptides interacting with the initial substrate docking site of gamma-secretase, suggesting a general strategy for the development of potent and specific inhibitors of intramembrane proteases...
  24. ncbi request reprint The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells
    Ayae Kinoshita
    Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 277:28530-6. 2002
    ..Thus, gamma secretase cleavage of APP may contribute to Alzheimer's disease-related neurodegeneration in two ways: release of amyloid-beta and liberation of a bioactive carboxyl-terminal domain from membrane-bound APP...
  25. pmc Inhibition of acyl-coenzyme A: cholesterol acyl transferase modulates amyloid precursor protein trafficking in the early secretory pathway
    Henri J Huttunen
    Neurobiology of Disease Laboratory, Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA
    FASEB J 23:3819-28. 2009
    ..Our results identify a novel ACAT-dependent mechanism that regulates secretory trafficking of APP, likely contributing to decreased Abeta generation in vivo...
  26. ncbi request reprint Gamma-secretase/presenilin inhibitors for Alzheimer's disease phenocopy Notch mutations in Drosophila
    Craig A Micchelli
    Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA
    FASEB J 17:79-81. 2003
    ....
  27. pmc Convergence of pathology in dementia with Lewy bodies and Alzheimer's disease: a role for the novel interaction of alpha-synuclein and presenilin 1 in disease
    Ashley R Winslow
    1 MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
    Brain 137:1958-70. 2014
    ....
  28. pmc Visualizing interaction of proteins relevant to Alzheimer's disease in intact cells
    Anne V Thomas
    Department of Neurology, University of Cologne, Germany
    Methods 44:299-303. 2008
    ....

Research Grants5

  1. Molecular mechanism of Presenilin-1 (PS1) linked Alzheimer's Disease pathology
    Oksana Berezovska; Fiscal Year: 2006
    ..More generally, the assay of monitoring PS1 conformation and y-secretase -substrate proximity will help to help develop methodologies that may prove useful in understanding disease-related protein conformation changes. ..
  2. Molecular mechanism of Presenilin-1 (PS1) linked Alzheimer's Disease pathology
    Oksana Berezovska; Fiscal Year: 2007
    ..More generally, the assay of monitoring PS1 conformation and y-secretase -substrate proximity will help to help develop methodologies that may prove useful in understanding disease-related protein conformation changes. ..
  3. Molecular mechanism of Presenilin-1 (PS1) linked Alzheimer's Disease pathology
    Oksana Berezovska; Fiscal Year: 2010
    ..More generally, the assay of monitoring PS1 conformation and y-secretase -substrate proximity will help to help develop methodologies that may prove useful in understanding disease-related protein conformation changes. ..
  4. Molecular mechanism of Presenilin-1 (PS1) linked Alzheimer's Disease pathology
    Oksana Berezovska; Fiscal Year: 2009
    ..More generally, the assay of monitoring PS1 conformation and y-secretase -substrate proximity will help to help develop methodologies that may prove useful in understanding disease-related protein conformation changes. ..