NIKOLAOS ROBAKIS

Summary

Affiliation: Mount Sinai School of Medicine
Country: USA

Publications

  1. doi request reprint Cell signaling abnormalities may drive neurodegeneration in familial Alzheimer disease
    Nikolaos K Robakis
    Departments of Psychiatry and Neuroscience, Mount Sinai School of Medicine, New York University, One Gustave Levy Pl, Box 1229, New York, NY, 10029, USA
    Neurochem Res 39:570-5. 2014
  2. pmc Mechanisms of AD neurodegeneration may be independent of Aβ and its derivatives
    Nikolaos K Robakis
    Department of Psychiatry, Mount Sinai School of Medicine, New York University, One Gustave Levy Pl Box 1229, New York, NY 10029, USA
    Neurobiol Aging 32:372-9. 2011
  3. ncbi request reprint An Alzheimer's disease hypothesis based on transcriptional dysregulation
    Nikolaos K Robakis
    Department of Psychiatry, Fishberg Reserch Center for Neurobiology, Mount Sinai School of Medicine, New York University, One Gustave L Levy Place, New York, NY 10029, USA
    Amyloid 10:80-5. 2003
  4. pmc Are Abeta and its derivatives causative agents or innocent bystanders in AD?
    Nikolaos K Robakis
    Center for Molecular Biology and Genetics of Neurodegeneration, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    Neurodegener Dis 7:32-7. 2010
  5. ncbi request reprint A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell 114:635-45. 2003
  6. pmc PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations
    Lia Baki
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    EMBO J 23:2586-96. 2004
  7. doi request reprint Wild-type but not FAD mutant presenilin-1 prevents neuronal degeneration by promoting phosphatidylinositol 3-kinase neuroprotective signaling
    Lia Baki
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Neurosci 28:483-90. 2008
  8. ncbi request reprint Cyclooxygenase (COX)-2 and COX-1 potentiate beta-amyloid peptide generation through mechanisms that involve gamma-secretase activity
    Weiping Qin
    Neuroinflammation Research Laboratories, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:50970-7. 2003
  9. pmc A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    EMBO J 21:1948-56. 2002
  10. ncbi request reprint Presenilin-1 is expressed in neural progenitor cells in the hippocampus of adult mice
    Paul H Wen
    Department of Psychiatry, P O Box 1229, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
    Neurosci Lett 318:53-6. 2002

Collaborators

Detail Information

Publications21

  1. doi request reprint Cell signaling abnormalities may drive neurodegeneration in familial Alzheimer disease
    Nikolaos K Robakis
    Departments of Psychiatry and Neuroscience, Mount Sinai School of Medicine, New York University, One Gustave Levy Pl, Box 1229, New York, NY, 10029, USA
    Neurochem Res 39:570-5. 2014
    ..Here we discuss evidence that FAD neurodegeneration may be caused by loss of γ-secretase cleavage function at ε sites of substrates. ..
  2. pmc Mechanisms of AD neurodegeneration may be independent of Aβ and its derivatives
    Nikolaos K Robakis
    Department of Psychiatry, Mount Sinai School of Medicine, New York University, One Gustave Levy Pl Box 1229, New York, NY 10029, USA
    Neurobiol Aging 32:372-9. 2011
    ....
  3. ncbi request reprint An Alzheimer's disease hypothesis based on transcriptional dysregulation
    Nikolaos K Robakis
    Department of Psychiatry, Fishberg Reserch Center for Neurobiology, Mount Sinai School of Medicine, New York University, One Gustave L Levy Place, New York, NY 10029, USA
    Amyloid 10:80-5. 2003
    ..This raises the possibility that, similar to polyglutamine induced neurodegeneration like Huntington's chorea, transcriptional abnormalities are involved in the development of FAD...
  4. pmc Are Abeta and its derivatives causative agents or innocent bystanders in AD?
    Nikolaos K Robakis
    Center for Molecular Biology and Genetics of Neurodegeneration, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    Neurodegener Dis 7:32-7. 2010
    ....
  5. ncbi request reprint A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell 114:635-45. 2003
    ..These data raise the possibility that FAD mutation-induced transcriptional abnormalities maybe causally related to the dementia associated with FAD...
  6. pmc PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations
    Lia Baki
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA
    EMBO J 23:2586-96. 2004
    ..Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway...
  7. doi request reprint Wild-type but not FAD mutant presenilin-1 prevents neuronal degeneration by promoting phosphatidylinositol 3-kinase neuroprotective signaling
    Lia Baki
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Neurosci 28:483-90. 2008
    ..These observations suggest that stimulation of PI3K/Akt signaling may be beneficial to FAD patients...
  8. ncbi request reprint Cyclooxygenase (COX)-2 and COX-1 potentiate beta-amyloid peptide generation through mechanisms that involve gamma-secretase activity
    Weiping Qin
    Neuroinflammation Research Laboratories, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:50970-7. 2003
    ....
  9. pmc A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions
    Philippe Marambaud
    Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    EMBO J 21:1948-56. 2002
    ..Thus, the PS1/gamma-secretase system stimulates disassembly of the E-cadherin- catenin complex and increases the cytosolic pool of beta-catenin, a key regulator of the Wnt signaling pathway...
  10. ncbi request reprint Presenilin-1 is expressed in neural progenitor cells in the hippocampus of adult mice
    Paul H Wen
    Department of Psychiatry, P O Box 1229, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
    Neurosci Lett 318:53-6. 2002
    ..Cells expressing PS-1 and the neural progenitor marker nestin were also found. Thus PS-1 is expressed in neural progenitor cells in adult hippocampus implying its possible role in neurogenesis in adult brain...
  11. ncbi request reprint Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice
    Paul H Wen
    Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
    Neurobiol Dis 10:8-19. 2002
    ..These studies suggest that PS-1 plays a role in regulating neurogenesis in adult hippocampus and that FAD mutants may have deleterious properties independent of their effects on amyloid deposition...
  12. ncbi request reprint The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice
    Paul H Wen
    Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Exp Neurol 188:224-37. 2004
    ..They also identify a new mechanism whereby PS1 FAD mutants may impair normal neuronal function and may have implications for the physiological functioning of the hippocampus in FAD...
  13. ncbi request reprint The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors
    Georgia Agiostratidou
    Department of Psychiatry, Mount Sinai School of Medicine, New York 10029, USA
    J Neurochem 96:1182-8. 2006
    ..In addition, E-Cad/CTF2 decreases accumulation of total secreted A beta. These data suggest a novel method to promote the non-amyloidogenic degradation of A beta precursors and to inhibit A beta production...
  14. pmc Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling
    Anastasios Georgakopoulos
    Department of Psychiatry, Mount Sinai School of Medicine, NYU, New York, NY 10029, USA
    EMBO J 25:1242-52. 2006
    ..PS1 FAD and gamma-secretase dominant-negative mutants inhibited the EphB-induced cleavage of ephrinB2 and Src autophosphorylation, raising the possibility that FAD mutants interfere with the functions of Src and ephrinB2 in the CNS...
  15. ncbi request reprint It may take inflammation, phosphorylation and ubiquitination to 'tangle' in Alzheimer's disease
    Lisette Arnaud
    Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10021, USA
    Neurodegener Dis 3:313-9. 2006
    ..In order to design therapies that will prevent endangered neurons from dying, it is critical that we learn more about the effects of neuroinflammation and its products...
  16. pmc Inhibitors of γ-secretase stabilize the complex and differentially affect processing of amyloid precursor protein and other substrates
    Gael Barthet
    Department of Psychiatry, Mt Sinai School of Medicine, New York University, New York, NY 10029, USA
    FASEB J 25:2937-46. 2011
    ..Furthermore, our observations have implications for GSIs as therapeutics because processing of functionally important substrates may be inhibited at lower concentrations than Aβ...
  17. ncbi request reprint Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor
    Claudia Litterst
    Department of Psychiatry and Neuroscience, Mount Sinai School of Medicine New York University, New York, NY 10029, USA, and Institute for Molecular Cardiovascular Research, University Hospital Reinisch West Faelische Technische Hochschule, Aachen, Germany
    J Biol Chem 282:16155-63. 2007
    ..Our data identify novel cleavages and modifications of EphB2 receptor and indicate that specific conditions determine the proteolytic systems and subcellular sites involved in the processing of this receptor...
  18. pmc Peptide EphB2/CTF2 generated by the gamma-secretase processing of EphB2 receptor promotes tyrosine phosphorylation and cell surface localization of N-methyl-D-aspartate receptors
    Jindong Xu
    Center for Molecular Biology and Genetics of Neurodegeneration, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 284:27220-8. 2009
    ..Because NMDAR plays central roles in synaptic plasticity and function, our results provide a potential link between the gamma-secretase function of presenilin 1 and learning and memory...
  19. ncbi request reprint Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability
    Geo Serban
    Department of Psychiatry, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA
    J Biol Chem 280:36007-12. 2005
    ..Thus, cadherins mediate both the association of PS1 and beta-catenin and the effects of PS1 on the cellular levels of beta-catenin...
  20. ncbi request reprint Novel processing of Notch 1 within its intracellular domain by a cysteine protease
    Angeliki Fassa
    Division of Animal and Human Physiology, Department of Biology, University of Athens, Athens, Greece
    Neurodegener Dis 4:148-55. 2007
    ..Processing of hN1 within its intracellular domain could generate fragments that can exert novel functions and/or interfere with the function of hN1 intracellular domain...
  21. ncbi request reprint The discovery and mapping to chromosome 21 of the Alzheimer's amyloid gene: history revised
    Nikolaos K Robakis
    J Alzheimers Dis 10:453-5. 2006

Research Grants27

  1. Cadherin-PS1-gamma-secretase signal transduction pathway
    NIKOLAOS ROBAKIS; Fiscal Year: 2005
    ..This application proposes to characterize the cadherin-PS1-gamma-secretase signal transduction pathway and to examine its involvement in Alzheimer's disease. ..
  2. Presenilin 1 (PS1) activates the PI3k/Akt cell survival pathway
    NIKOLAOS ROBAKIS; Fiscal Year: 2007
    ....
  3. PS1 regulates processing and signaling of ephrinB/EphB
    NIKOLAOS ROBAKIS; Fiscal Year: 2007
    ..Here we propose to elucidate the mechanism by which PS1 regulates signaling events triggered by the EphB2/ephrinB2 interaction. We will also examine the effects of FAD-linked PS1 mutations on these signaling events. ..
  4. Cadherin/PS1/P123K/Akt signaling in neuronal survival and AD
    NIKOLAOS ROBAKIS; Fiscal Year: 2007
    ..Finally, we will identify adaptor molecules promoting the PS1/cadherin/PI3K complex. ..
  5. PS1 mediates the neuroprotective functions of the ephrinB/EphB system
    NIKOLAOS ROBAKIS; Fiscal Year: 2009
    ..Our findings have implications for the mechanisms by which genetic mutations cause neurodegeneration and may provide novel targets for therapeutic intervention in AD. ..
  6. PS1 mediates the neuroprotective functions of the ephrinB/EphB system
    Nikolaos K Robakis; Fiscal Year: 2010
    ..Our findings have implications for the mechanisms by which genetic mutations cause neurodegeneration and may provide novel targets for therapeutic intervention in AD. ..
  7. PRESENILIN 1 IS A COMPONENT OF THE ADHERENS JUNCTIONS
    NIKOLAOS ROBAKIS; Fiscal Year: 2004
    ..Finally, we will examine whether PS1 is part of the cadherin/catenin apparatus at the synapse. ..
  8. PRODUCTION OF CYTOPLASMIC DOMAIN CONTAINING SOLUBLE APP
    NIKOLAOS ROBAKIS; Fiscal Year: 2000
    ..The study will elucidate the structure of solAPPcyt and the mechanism of its production and secretion, and will examine its relationship to AD and A-beta. ..
  9. Cadherin/PS1/P123K/Akt signaling in neuronal survival and AD
    Nikolaos K Robakis; Fiscal Year: 2010
    ..Finally, we will identify adaptor molecules promoting the PS1/cadherin/PI3K complex. ..