Kenneth S Kosik

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Phosphorylated tau and the neurodegenerative foldopathies
    Kenneth S Kosik
    Department of Neurology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Biochim Biophys Acta 1739:298-310. 2005
  2. ncbi request reprint Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation
    Jae Suk Ahn
    Department of Neurology and Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Chem Biol 12:811-23. 2005
  3. ncbi request reprint Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, tau
    Deguang Zhu
    Renal Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    J Biol Chem 279:54983-6. 2004
  4. ncbi request reprint Delta-catenin at the synaptic-adherens junction
    Kenneth S Kosik
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Trends Cell Biol 15:172-8. 2005
  5. ncbi request reprint Wnt-1 expression in PC12 cells induces exon 15 deletion and expression of L-APP
    Peter J Morin
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Dis 16:59-67. 2004
  6. pmc Specific microRNAs modulate embryonic stem cell-derived neurogenesis
    Anna M Krichevsky
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Stem Cells 24:857-64. 2006
  7. ncbi request reprint Binding of tau to heat shock protein 27 leads to decreased concentration of hyperphosphorylated tau and enhanced cell survival
    Hideki Shimura
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:17957-62. 2004
  8. ncbi request reprint CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival
    Hideki Shimura
    Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 279:4869-76. 2004
  9. ncbi request reprint Development of an assay to screen for inhibitors of tau phosphorylation by cdk5
    Jae Suk Ahn
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, USA
    J Biomol Screen 9:122-31. 2004
  10. pmc Attenuated hippocampus-dependent learning and memory decline in transgenic TgAPPswe Fischer-344 rats
    Nelson Ruiz-Opazo
    Section of Molecular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Mol Med 10:36-44. 2004

Collaborators

Detail Information

Publications42

  1. ncbi request reprint Phosphorylated tau and the neurodegenerative foldopathies
    Kenneth S Kosik
    Department of Neurology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Biochim Biophys Acta 1739:298-310. 2005
    ....
  2. ncbi request reprint Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation
    Jae Suk Ahn
    Department of Neurology and Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Chem Biol 12:811-23. 2005
    ..These leads could be a starting point for structure-based drug design of more potent and selective inhibitors...
  3. ncbi request reprint Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, tau
    Deguang Zhu
    Renal Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    J Biol Chem 279:54983-6. 2004
    ..Taken together, these findings reveal novel, direct regulation of PP2A activity by Galpha(12) and potential in vivo modulation of PP2A target proteins including tau...
  4. ncbi request reprint Delta-catenin at the synaptic-adherens junction
    Kenneth S Kosik
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Trends Cell Biol 15:172-8. 2005
    ..Taken together, recent evidence indicates that delta-catenin is a sensor of synaptic activity and implements activity-related morphological changes at the synapse...
  5. ncbi request reprint Wnt-1 expression in PC12 cells induces exon 15 deletion and expression of L-APP
    Peter J Morin
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Dis 16:59-67. 2004
    ..In PC12 cells, Wnt-1 expression is associated with induction of exon 15 deletion from APP mRNA and expression of L-APP. Our data suggest that APP isoform expression is regulated, in part, by the Wnt/wingless signaling pathway...
  6. pmc Specific microRNAs modulate embryonic stem cell-derived neurogenesis
    Anna M Krichevsky
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Stem Cells 24:857-64. 2006
    ..We conclude that distinct miRNAs play a functional role in the determination of neural fates in ES cell differentiation...
  7. ncbi request reprint Binding of tau to heat shock protein 27 leads to decreased concentration of hyperphosphorylated tau and enhanced cell survival
    Hideki Shimura
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:17957-62. 2004
    ..Moreover, Hsp27 rescues pathological hyperphosphorylated tau-mediated cell death. Therefore, Hsp27 is likely to provide a neuroprotective effect in AD and other tauopathies...
  8. ncbi request reprint CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival
    Hideki Shimura
    Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 279:4869-76. 2004
    ..CHIP could rescue phosphorylated tau-induced cell death, and therefore the CHIP-Hsc70 complex may provide a new therapeutic target for the tauopathies...
  9. ncbi request reprint Development of an assay to screen for inhibitors of tau phosphorylation by cdk5
    Jae Suk Ahn
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, USA
    J Biomol Screen 9:122-31. 2004
    ..The performance of this assay in a high-throughput format was demonstrated and used to identify inhibitors of tau phosphorylation at specific epitopes phosphorylated by cdk5/p25...
  10. pmc Attenuated hippocampus-dependent learning and memory decline in transgenic TgAPPswe Fischer-344 rats
    Nelson Ruiz-Opazo
    Section of Molecular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Mol Med 10:36-44. 2004
    ..The data support the hypothesis that a threshold paradigm underlies Abeta-related pathology, below which APP expression may play a physiological role in specific hippocampus-dependent tasks, most likely related to its neurotrophic role...
  11. pmc MicroRNA profiling of the murine hematopoietic system
    Silvia Monticelli
    Department of Pathology, Harvard Medical School, and CBR Institute for Biomedical Research, Boston, MA 02115, USA
    Genome Biol 6:R71. 2005
    ..It is becoming clear that miRNAs play an important role in the regulation of gene expression during development. However, in mammals, expression data are principally based on whole tissue analysis and are still very incomplete...
  12. pmc Growth hormone is produced within the hippocampus where it responds to age, sex, and stress
    Christine P Donahue
    Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:6031-6. 2006
    ..These results suggest that GH may be involved in functions ascribed to the hippocampus, such as learning and the response to stressful experience...
  13. ncbi request reprint The mammalian RNA-binding protein Staufen2 links nuclear and cytoplasmic RNA processing pathways in neurons
    Michaela Monshausen
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neuromolecular Med 6:127-44. 2004
    ..We suggest a model whereby a set of conserved genes in the oskar mRNA export pathway may be recruited to direct a dendritic destination for mRNAs originating as a Staufen2 nuclear complex...
  14. ncbi request reprint New approaches to the discovery of cdk5 inhibitors
    Marcie A Glicksman
    Laboratory for Drug Discovery for Neurodegeneration, Harvard Center for Neurodegeneration and Repair, Brigham and Women s Hospital and Harvard Medical School, Cambridge, MA, USA
    Curr Alzheimer Res 4:547-9. 2007
    ..The hope is that non-ATP competitive compounds will more likely be selective and will be better therapeutics...
  15. pmc RNAi functions in cultured mammalian neurons
    Anna M Krichevsky
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:11926-9. 2002
    ..We report here an application of RNAi to postmitotic primary neuronal cultures. Synthetic siRNA can be readily introduced into neurons and effectively inhibit the expression of endogenous and transfected genes...
  16. pmc Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies
    Michael G Schlossmacher
    Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Am J Pathol 160:1655-67. 2002
    ..These results suggest that functional parkin proteins may be required during LB formation...
  17. ncbi request reprint The message and the messenger: delivering RNA in neurons
    Kenneth S Kosik
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Sci STKE 2002:pe16. 2002
    ..Kosik and Krichevsky describe how a dynamic macromolecular structure, the RNA granule, may be a key element contributing to changes in protein production leading to synaptic plasticity...
  18. ncbi request reprint CADASIL mutations impair Notch3 glycosylation by Fringe
    Joseph F Arboleda-Velasquez
    Neurology Department, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Hum Mol Genet 14:1631-9. 2005
    ..CADASIL changes also induced aberrant homodimerization of mutant Notch3 fragments and heterodimerization of mutant Notch3 with Lunatic Fringe itself. Together, these data suggest that Fringe plays a role in CADASIL pathophysiology...
  19. pmc A microRNA array reveals extensive regulation of microRNAs during brain development
    Anna M Krichevsky
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    RNA 9:1274-81. 2003
    ..Creating clusters of coexpressed miRNAs will contribute to understanding their regulation, functions, and discovery of mRNA targets...
  20. pmc Identification of many microRNAs that copurify with polyribosomes in mammalian neurons
    John Kim
    Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 101:360-5. 2004
    ..Moreover, all of the miRNAs that were tested cofractionate with polyribosomes, the sites of active translation. These findings indicate that a large, diverse population of miRNAs may function to regulate translation in mammalian neurons...
  21. pmc Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho
    Maria Cruz Martinez
    Dept of Neurology, Brigham and Women s Hospital and Harvard Medical School, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    J Cell Biol 162:99-111. 2003
    ..We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree...
  22. ncbi request reprint MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells
    Jennifer A Chan
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:6029-33. 2005
    ..Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes...
  23. pmc Stabilization of the tau exon 10 stem loop alters pre-mRNA splicing
    Christine P Donahue
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:23302-6. 2006
    ..Together these results validate the stem loop as a bona fide structure regulating tau exon 10 splicing...
  24. ncbi request reprint Distribution pattern of Notch3 mutations suggests a gain-of-function mechanism for CADASIL
    Christine P Donahue
    Department of Neurology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Genomics 83:59-65. 2004
    ....
  25. ncbi request reprint Discovery of compounds that will prevent tau pathology
    Kenneth S Kosik
    Harvard Medical School, Brigham and Women s Hospital, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    J Mol Neurosci 19:261-6. 2002
    ..We have designed a moderate throughput for tau binding that relies on fluorescence detection in living cells and an in vitro cdk5/p25 tau phosphorylation high throughput screen...
  26. ncbi request reprint BACE1 suppression by RNA interference in primary cortical neurons
    Shih Chu Kao
    Department of Pathology, Harvard Medical School and Howard Hughes Medical Institute, Armenise Building, 200 Longwood Avenue, Boston, MA 02115, USA
    J Biol Chem 279:1942-9. 2004
    ..Our results indicate that BACE1 siRNA specifically impacts on beta-cleavage of APP and may be a potential therapeutic approach for treating AD...
  27. ncbi request reprint Beyond phrenology, at last
    Kenneth S Kosik
    Department of Neurology, Harvard Medical School and at the Brigham and Women s Hospital, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Rev Neurosci 4:234-9. 2003
    ....
  28. pmc Transcriptional profiling reveals regulated genes in the hippocampus during memory formation
    Christine P Donahue
    Department of Neurology, Center for Neurologic Disease, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Hippocampus 12:821-33. 2002
    ..These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories...
  29. ncbi request reprint The neuronal microRNA system
    Kenneth S Kosik
    Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA
    Nat Rev Neurosci 7:911-20. 2006
    ..Nevertheless, the identification of such targets promises to provide new insights into many facets of neuronal function...
  30. ncbi request reprint Development of a fluorescent high throughput assay for tau aggregation
    Min Liu
    Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women s Hospital and Harvard Medical School, Cambridge, MA, USA
    Assay Drug Dev Technol 2:609-19. 2004
    ..A model for tau aggregation is presented. The performance of this assay in a high throughput format is demonstrated and can be used to identify inhibitors of tau aggregation...
  31. pmc MicroRNAs: regulators of oncogenesis and stemness
    Thales Papagiannakopoulos
    BMC Med 6:15. 2008
    ..In this commentary, we discuss the known functions of miRNAs in cancer and stem cells, their therapeutic potential and how the findings of Silber et al provide insight into the role of miR-124/miR-137 dysregulation in glioblastomas...
  32. pmc Highly conserved O-fucose sites have distinct effects on Notch1 function
    Raajit Rampal
    Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, Stony Brook University, New York 11794 5215, USA
    J Biol Chem 280:32133-40. 2005
    ..These results indicate that the most highly conserved O-fucose sites in Notch1 are important for both processing and ligand-mediated signaling in the context of a cell-based signaling assay...
  33. ncbi request reprint Synaptic tagging -- who's it?
    Kelsey C Martin
    Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, University of California, Los Angeles, 695 Charles Young Drive South, Los Angeles, California 90095 1761, USA
    Nat Rev Neurosci 3:813-20. 2002
  34. pmc Somatodendritic microRNAs identified by laser capture and multiplex RT-PCR
    Min Jeong Kye
    Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, CA 93106, USA
    RNA 13:1224-34. 2007
    ..A very small number of miRNAs deviate from the distribution gradient across the miRNA population as relatively enriched or depleted in the dendrite...
  35. ncbi request reprint The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF
    Richard P Laura
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    J Biol Chem 277:12906-14. 2002
    ..They also demonstrate that C-terminal phage-display technology can be used to predict physiologically relevant ligands for PDZ domains...
  36. ncbi request reprint Traveling the tau pathway: a personal account
    Kenneth S Kosik
    Neuroscience Research Institute, Dept of Molecular and Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106 5060, USA
    J Alzheimers Dis 9:251-6. 2006
    ..For most the vindication of this tireless effort will come from tau-based therapies; but for others the remarkable biology revealed by the Alzheimer disease process has been its own reward...
  37. ncbi request reprint Spatial learning and memory is preserved in rats after early development in a microgravity environment
    Meredith D Temple
    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 9525, USA
    Neurobiol Learn Mem 78:199-216. 2002
    ..Any differences due to development in microgravity are quickly reversed after return to earth normal gravity...
  38. ncbi request reprint Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction
    Inbal Israely
    Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA
    Curr Biol 14:1657-63. 2004
    ....
  39. ncbi request reprint Neuroscience gears up for duel on the issue of brain versus deity
    Kenneth S Kosik
    Nature 439:138. 2006
  40. ncbi request reprint Activation of the neuronal c-Abl tyrosine kinase by amyloid-beta-peptide and reactive oxygen species
    Alejandra R Alvarez
    FONDAP Center for Cell and Molecular Biology Joaquin V Luco, P Universidad Catolica de Chile, Santiago, 114 D, Chile
    Neurobiol Dis 17:326-36. 2004
    ..These results directly point to a therapeutic strategy for the treatment of Alzheimer's disease...
  41. ncbi request reprint The Elegance of the MicroRNAs: A Neuronal Perspective
    Kenneth S Kosik
    Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, California 93106, USA
    Neuron 47:779-82. 2005
    ..This review examines the interface between an emerging biology of miRNAs and their role in nervous systems...
  42. ncbi request reprint Teaching resources. A model for local regulation of translation near active synapses
    Kenneth S Kosik
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106 5060, USA
    Sci STKE 2005:tr25. 2005
    ....