Gal Bitan

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies
    Marina D Kirkitadze
    Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
    J Neurosci Res 69:567-77. 2002
  2. pmc Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:330-5. 2003
  3. ncbi request reprint Elucidation of primary structure elements controlling early amyloid beta-protein oligomerization
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:34882-9. 2003
  4. pmc Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease
    Alon Monsonego
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 112:415-22. 2003
  5. ncbi request reprint A molecular switch in amyloid assembly: Met35 and amyloid beta-protein oligomerization
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Am Chem Soc 125:15359-65. 2003
  6. ncbi request reprint Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by " molecular tweezers" - from the test tube to animal models
    AIDA ATTAR
    Department of Neurology, David Geffen School of Medicine at UCLA, Neuroscience Research Building 1, Room 451, 635 Charles E Young Drive South, Los Angeles, CA 90095 7334, USA
    Curr Pharm Des 20:2469-83. 2014
  7. pmc RNA aptamers generated against oligomeric Abeta40 recognize common amyloid aptatopes with low specificity but high sensitivity
    Farid Rahimi
    Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
    PLoS ONE 4:e7694. 2009
  8. pmc A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease
    AIDA ATTAR
    Department of Neurology, University of California Los Angeles, Los Angeles, California, United States of America Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 8:e80355. 2013
  9. doi request reprint Safety and pharmacological characterization of the molecular tweezer CLR01 - a broad-spectrum inhibitor of amyloid proteins' toxicity
    AIDA ATTAR
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 7334, USA
    BMC Pharmacol Toxicol 15:23. 2014
  10. pmc Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers
    AIDA ATTAR
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Neuroscience Research Building 1, Room 451, 635 Charles E Young Drive South, Los Angeles, CA 90095 7334, USA
    Brain 135:3735-48. 2012

Research Grants

  1. Novel Specific Ligands for ABeta Oligomers
    Gal Bitan; Fiscal Year: 2007

Collaborators

Detail Information

Publications38

  1. ncbi request reprint Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies
    Marina D Kirkitadze
    Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
    J Neurosci Res 69:567-77. 2002
    ..The archetypal features of the assembly-dependent neuropathogenetic effects of Abeta may thus be of relevance not only to AD but to these other disorders as well...
  2. pmc Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:330-5. 2003
    ..The strong etiologic association of Abeta42 with AD may thus be a result of assemblies formed at the earliest stages of peptide oligomerization...
  3. ncbi request reprint Elucidation of primary structure elements controlling early amyloid beta-protein oligomerization
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital, and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:34882-9. 2003
    ..These results reveal how specific regions and residues control A beta oligomerization and show that these controlling elements differ between A beta 40 and A beta 42...
  4. pmc Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease
    Alon Monsonego
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 112:415-22. 2003
    ....
  5. ncbi request reprint A molecular switch in amyloid assembly: Met35 and amyloid beta-protein oligomerization
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Am Chem Soc 125:15359-65. 2003
    ..Preventing assembly of toxic Abeta42 paranuclei through selective oxidation of Met(35) thus represents a potential therapeutic approach for AD...
  6. ncbi request reprint Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by " molecular tweezers" - from the test tube to animal models
    AIDA ATTAR
    Department of Neurology, David Geffen School of Medicine at UCLA, Neuroscience Research Building 1, Room 451, 635 Charles E Young Drive South, Los Angeles, CA 90095 7334, USA
    Curr Pharm Des 20:2469-83. 2014
    ....
  7. pmc RNA aptamers generated against oligomeric Abeta40 recognize common amyloid aptatopes with low specificity but high sensitivity
    Farid Rahimi
    Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
    PLoS ONE 4:e7694. 2009
    ..Nevertheless, the high sensitivity, whereby aptamers detect beta-sheet formation, suggests that they can serve as superior amyloid recognition tools...
  8. pmc A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease
    AIDA ATTAR
    Department of Neurology, University of California Los Angeles, Los Angeles, California, United States of America Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 8:e80355. 2013
    ....
  9. doi request reprint Safety and pharmacological characterization of the molecular tweezer CLR01 - a broad-spectrum inhibitor of amyloid proteins' toxicity
    AIDA ATTAR
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 7334, USA
    BMC Pharmacol Toxicol 15:23. 2014
    ..With the goal of developing CLR01 as a therapeutic drug for Alzheimer's disease and other amyloidoses, here we studied its safety and pharmacokinetics...
  10. pmc Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers
    AIDA ATTAR
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Neuroscience Research Building 1, Room 451, 635 Charles E Young Drive South, Los Angeles, CA 90095 7334, USA
    Brain 135:3735-48. 2012
    ..The efficacy and toxicity results support a process-specific mechanism of action of molecular tweezers and suggest that these are promising compounds for developing disease-modifying therapy for Alzheimer's disease and related disorders...
  11. ncbi request reprint Neurotoxic protein oligomers--what you see is not always what you get
    Gal Bitan
    Department of Neurology, David Geffen School of Medicine at UCLA, 90095 7334, USA
    Amyloid 12:88-95. 2005
    ....
  12. pmc Biophysical characterization of Abeta42 C-terminal fragments: inhibitors of Abeta42 neurotoxicity
    Huiyuan Li
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 635 Charles E Young Drive, Los Angeles, California 90095, USA
    Biochemistry 49:1259-67. 2010
    ..The data enhance our understanding of the physical characteristics that affect CTF activity and advance our ability to design, synthesize, and test future generations of inhibitors...
  13. pmc Comparison of three amyloid assembly inhibitors: the sugar scyllo-inositol, the polyphenol epigallocatechin gallate, and the molecular tweezer CLR01
    Sharmistha Sinha
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
    ACS Chem Neurosci 3:451-8. 2012
    ....
  14. pmc Mechanistic investigation of the inhibition of Abeta42 assembly and neurotoxicity by Abeta42 C-terminal fragments
    Huiyuan Li
    Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, 635 Charles E Young Drive S, Los Angeles, CA 90095, USA
    Biochemistry 49:6358-64. 2010
    ....
  15. pmc C-terminal peptides coassemble into Abeta42 oligomers and protect neurons against Abeta42-induced neurotoxicity
    Erica A Fradinger
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 105:14175-80. 2008
    ..Thus, Abeta(31-42) and Abeta(39-42) are leads for obtaining mechanism-based drugs for treatment of AD using a systematic structure-activity approach...
  16. pmc Despite its role in assembly, methionine 35 is not necessary for amyloid beta-protein toxicity
    Panchanan Maiti
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
    J Neurochem 113:1252-62. 2010
    ....
  17. pmc C-terminal tetrapeptides inhibit Aβ42-induced neurotoxicity primarily through specific interaction at the N-terminus of Aβ42
    Huiyuan Li
    Department of Neurology, David Geffen School of Medicine, Brain Research Institute, University of California, Los Angeles, 635 Charles E Young Drive South, Los Angeles, California 90095 7334, United States
    J Med Chem 54:8451-60. 2011
    ....
  18. pmc A two-step strategy for structure-activity relationship studies of N-methylated aβ42 C-terminal fragments as aβ42 toxicity inhibitors
    Huiyuan Li
    Department of Neurology, David Geffen School of Medicine, University of California Los Angeles UCLA, 635 Charles E Young Drive S, Los Angeles, CA 90095, USA
    ChemMedChem 7:515-22. 2012
    ....
  19. pmc A key role for lysine residues in amyloid β-protein folding, assembly, and toxicity
    Sharmistha Sinha
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA
    ACS Chem Neurosci 3:473-81. 2012
    ....
  20. pmc Amino acid position-specific contributions to amyloid beta-protein oligomerization
    Samir K Maji
    Department of Neurology, UCLA, Los Angeles, California 90095, USA
    J Biol Chem 284:23580-91. 2009
    ....
  21. pmc Structural study of metastable amyloidogenic protein oligomers by photo-induced cross-linking of unmodified proteins
    Gal Bitan
    UCLA, Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA
    Methods Enzymol 413:217-36. 2006
    ....
  22. pmc A novel "molecular tweezer" inhibitor of α-synuclein neurotoxicity in vitro and in vivo
    Shubhangi Prabhudesai
    Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA
    Neurotherapeutics 9:464-76. 2012
    ..Treatment with CLR01 almost completely mitigated the proteasome inhibition. The data suggest that CLR01 is a promising therapeutic agent for the treatment of Parkinson's disease and other synucleinopathies...
  23. doi request reprint Modulating self-assembly of amyloidogenic proteins as a therapeutic approach for neurodegenerative diseases: strategies and mechanisms
    Tingyu Liu
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 635 Charles E Young Drive South NRB 455, Los Angeles, CA 90095, USA
    ChemMedChem 7:359-74. 2012
    ..The merit of each strategy is assessed, and the key points to consider when analyzing the efficacy of possible drug candidates and their mechanism of action are discussed...
  24. ncbi request reprint En route to early diagnosis of Alzheimer's disease--are we there yet?
    Erica A Fradinger
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Trends Biotechnol 23:531-3. 2005
    ..This assay appears to be more specific for AD than previous ELISA-based work and, if specificity of the assay for Abeta oligomers can be established, the method developed might provide a sensitive, reliable diagnostic tool for AD...
  25. pmc Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins
    Sharmistha Sinha
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
    J Am Chem Soc 133:16958-69. 2011
    ..The data suggest that molecular tweezers are unique, process-specific inhibitors of aberrant protein aggregation and toxicity, which hold promise for developing disease-modifying therapy for amyloidoses...
  26. doi request reprint Preparation of stable amyloid β-protein oligomers of defined assembly order
    Clark Rosensweig
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Methods Mol Biol 849:23-31. 2012
    ..This method has been used successfully to provide material for formal structure-activity studies of Aβ oligomers...
  27. ncbi request reprint Elucidating amyloid beta-protein folding and assembly: A multidisciplinary approach
    David B Teplow
    Department of Neurology, David Geffen School of Medicine, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
    Acc Chem Res 39:635-45. 2006
    ..An integrated multidisciplinary program is required. We discuss here the synergistic application of in hydro, in vacuo, and in silico methods to the study of the amyloid beta-protein, the key pathogenetic agent in Alzheimer's disease...
  28. pmc Plasma methionine sulfoxide in persons with familial Alzheimer's disease mutations
    John M Ringman
    Mary S Easton Center for Alzheimer s Disease Research, Department of Neurology, University of California at Los Angeles, Los Angeles, CA 90095 7334, USA
    Dement Geriatr Cogn Disord 33:219-25. 2012
    ..We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) was increased in plasma proteins of persons carrying familial AD (FAD) mutations...
  29. doi request reprint Surprising toxicity and assembly behaviour of amyloid β-protein oxidized to sulfone
    Panchanan Maiti
    Department of Neurology, University of California at Los Angeles, 90025, USA
    Biochem J 433:323-32. 2011
    ..These surprising data decouple the toxicity of oxidized Aβ from its initial oligomerization, and suggest that our current understanding of the effect of methionine oxidation in Aβ is limited...
  30. doi request reprint Application of photochemical cross-linking to the study of oligomerization of amyloidogenic proteins
    Dahabada H J Lopes
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Methods Mol Biol 849:11-21. 2012
    ..The method has provided insights into the factors controlling early oligomerization, which could not be obtained by other means. We discuss sample preparation, experimental details, optimization of parameters, and troubleshooting...
  31. pmc Early diagnostics and therapeutics for Alzheimer's disease--how early can we get there?
    Bernhard H Monien
    Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Neuroscience Research Building 1, Room 455, 635 Charles E Young Drive South Los Angeles, CA 90095 7334, USA
    Expert Rev Neurother 6:1293-306. 2006
    ..Nevertheless, new insights into the earliest events that lead to development of AD increase hope that reliable diagnostics and efficacious therapies may emerge...
  32. ncbi request reprint Amyloid beta-protein: monomer structure and early aggregation states of Abeta42 and its Pro19 alloform
    Summer L Bernstein
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106 9501, USA
    J Am Chem Soc 127:2075-84. 2005
    ..These results are consistent with recently published photochemical cross-linking data and lend support to recent aggregation mechanisms proposed by Bitan, Teplow, and co-workers [J. Biol. Chem. 2003, 278, 34882-34889]...
  33. ncbi request reprint Preparation of aggregate-free, low molecular weight amyloid-beta for assembly and toxicity assays
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 299:3-9. 2005
    ..In this chapter, we describe the preparation of LMW Abeta using size exclusion chromatography and filtration. The advantages and disadvantages of each method are discussed...
  34. ncbi request reprint Determination of Peptide oligomerization state using rapid photochemical crosslinking
    Sabrina S Vollers
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 299:11-8. 2005
    ..PICUP provides a snapshot of the native oligomerization state of proteins and can be used for assembly state analysis of a wide variety of peptides and proteins...
  35. pmc Amyloid beta-protein monomer structure: a computational and experimental study
    Andrij Baumketner
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106 9501, USA
    Protein Sci 15:420-8. 2006
    ..Implications of the calculations on the early stages of aggregation of Abeta42 are discussed...
  36. ncbi request reprint Dendrimeric Abeta1-15 is an effective immunogen in wildtype and APP-tg mice
    Timothy J Seabrook
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, United States
    Neurobiol Aging 28:813-23. 2007
    ..Anti-Abeta antibodies bound monomeric, oligomeric, and fibrillar Abeta. Our data suggest that dAbeta1-15 may be an effective and potentially safer immunogen for Alzheimer's disease (AD) vaccination...
  37. ncbi request reprint Rapid photochemical cross-linking--a new tool for studies of metastable, amyloidogenic protein assemblies
    Gal Bitan
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Acc Chem Res 37:357-64. 2004
    ..The method provides essential insights into the factors that control the assembly of pathogenic protein oligomers, facilitating efforts toward the development of therapeutic agents...

Research Grants2

  1. Novel Specific Ligands for ABeta Oligomers
    Gal Bitan; Fiscal Year: 2007
    ....