Hilal A Lashuel

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint In vitro preparation of prefibrillar intermediates of amyloid-beta and alpha-synuclein
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 299:19-33. 2005
  2. ncbi request reprint New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Cambridge, Massachusetts 02139, USA
    J Biol Chem 277:42881-90. 2002
  3. ncbi request reprint Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils, including amyloid pores
    Hilal A Lashuel
    Harvard Center for Neurodegeneration and Repair, 65 Landsdowne St, Cambridge, MA 02139, USA
    J Mol Biol 332:795-808. 2003
  4. ncbi request reprint Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Cambridge, MA 02139, USA
    J Mol Biol 322:1089-102. 2002
  5. ncbi request reprint The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states
    Ross A Fredenburg
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Biochemistry 46:7107-18. 2007
  6. ncbi request reprint Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions
    Terunaga Nakagawa
    The Picower Center for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Neuron 44:453-67. 2004
  7. ncbi request reprint Interactions among alpha-synuclein, dopamine, and biomembranes: some clues for understanding neurodegeneration in Parkinson's disease
    Jean Christophe Rochet
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Cambridge, MA 02139, USA
    J Mol Neurosci 23:23-34. 2004
  8. ncbi request reprint A century-old debate on protein aggregation and neurodegeneration enters the clinic
    Peter T Lansbury
    Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Nature 443:774-9. 2006
  9. ncbi request reprint Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line
    Yichin Liu
    Center for Neurologic Diseases, Brigham and Women s Hospital, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Chem Biol 10:837-46. 2003
  10. ncbi request reprint The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility
    Yichin Liu
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Cambridge, MA 02139, USA
    Cell 111:209-18. 2002

Collaborators

Detail Information

Publications28

  1. ncbi request reprint In vitro preparation of prefibrillar intermediates of amyloid-beta and alpha-synuclein
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 299:19-33. 2005
    ....
  2. ncbi request reprint New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Cambridge, Massachusetts 02139, USA
    J Biol Chem 277:42881-90. 2002
    ..The inhibitory properties of the compounds presented suggest a new class of small molecules that could serve as a scaffold for the design of more efficient inhibitors of Abeta amyloidogenesis in vivo...
  3. ncbi request reprint Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils, including amyloid pores
    Hilal A Lashuel
    Harvard Center for Neurodegeneration and Repair, 65 Landsdowne St, Cambridge, MA 02139, USA
    J Mol Biol 332:795-808. 2003
    ..An increase in the ratio of Abeta(WT)/Abeta(MUT(Arctic)), therefore, may result in the accumulation of potential neurotoxic protofibrils and acceleration of disease progression in familial Alzheimer's disease mutation carriers...
  4. ncbi request reprint Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Cambridge, MA 02139, USA
    J Mol Biol 322:1089-102. 2002
    ..The formation of pore-like oligomeric structures may explain the membrane permeabilization activity of alpha-synuclein protofibrils. These structures may contribute to the pathogenesis of PD...
  5. ncbi request reprint The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states
    Ross A Fredenburg
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Biochemistry 46:7107-18. 2007
    ....
  6. ncbi request reprint Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions
    Terunaga Nakagawa
    The Picower Center for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Neuron 44:453-67. 2004
    ..Thus SAP97 has a broader role than its close relative, PSD-95, in the maintenance of synaptic function...
  7. ncbi request reprint Interactions among alpha-synuclein, dopamine, and biomembranes: some clues for understanding neurodegeneration in Parkinson's disease
    Jean Christophe Rochet
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Cambridge, MA 02139, USA
    J Mol Neurosci 23:23-34. 2004
    ..These variants might be useful to test whether membrane binding by alpha-synuclein is necessary for neurodegeneration in transgenic animal models of PD...
  8. ncbi request reprint A century-old debate on protein aggregation and neurodegeneration enters the clinic
    Peter T Lansbury
    Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Nature 443:774-9. 2006
    ..The clinical trials could also settle the century-old debate about causality...
  9. ncbi request reprint Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line
    Yichin Liu
    Center for Neurologic Diseases, Brigham and Women s Hospital, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Chem Biol 10:837-46. 2003
    ..The molecular mechanism of this response remains to be determined...
  10. ncbi request reprint The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility
    Yichin Liu
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Cambridge, MA 02139, USA
    Cell 111:209-18. 2002
    ..Thus, the ligase activity as well as the hydrolase activity of UCH-L1 may play a role in proteasomal protein degradation, a critical process for neuronal health...
  11. ncbi request reprint Neurodegenerative disease: amyloid pores from pathogenic mutations
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    Nature 418:291. 2002
    ....
  12. ncbi request reprint Molecular electron microscopy approaches to elucidating the mechanisms of protein fibrillogenesis
    Hilal A Lashuel
    Center for Neurologic Diseases, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 299:81-101. 2005
    ..An overview of the strength and limitations of these techniques as tools for elucidating the structural basis of amyloid fibril formation will be presented...
  13. 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...
  14. ncbi request reprint Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis
    Gabriele Tuchscherer
    Institute of Chemical Sciences and Engineering, Ecole Polytechnique Federale de Lausanne, EPFL, CH 1015 Lausanne, Switzerland
    Biopolymers 88:239-52. 2007
    ....
  15. ncbi request reprint Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins?
    Hilal A Lashuel
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Q Rev Biophys 39:167-201. 2006
    ..The purpose of this review is to summarize the existing supportive circumstantial evidence and to stimulate further studies designed to test the validity of this hypothesis...
  16. ncbi request reprint Lead (Pb) exposure and its effect on APP proteolysis and Abeta aggregation
    Md Riyaz Basha
    Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
    FASEB J 19:2083-4. 2005
    ..The aforementioned results provide further evidence for the developmental basis of amyloidogenesis and late-life disturbances in AD-associated proteins by environmental agents...
  17. ncbi request reprint Branched KLVFF tetramers strongly potentiate inhibition of beta-amyloid aggregation
    Sidhartha M Chafekar
    Neurogenetics Laboratory, Academic Medical Center, P O Box 22660, 1100 DD Amsterdam, The Netherlands
    Chembiochem 8:1857-64. 2007
    ..Our data lead us to propose that conjugates that bear multiple copies of KLVFF might be useful as therapeutic agents for the treatment of Alzheimer's disease...
  18. ncbi request reprint Membrane permeabilization: a common mechanism in protein-misfolding diseases
    Hilal A Lashuel
    Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Ecole Polytechnique Federale de Lausanne EPFL, CH 1015 Lausanne, Switzerland
    Sci Aging Knowledge Environ 2005:pe28. 2005
    ..quot;..
  19. pmc Murine apolipoprotein serum amyloid A in solution forms a hexamer containing a central channel
    Limin Wang
    Department of Chemistry, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA
    Proc Natl Acad Sci U S A 99:15947-52. 2002
    ..1 forms a membrane channel and have important implications for understanding the 3D structure, multiple functions, and pathological roles of this highly conserved protein...
  20. ncbi request reprint Disruption of amyloid-derived peptide assemblies through the controlled induction of a beta-sheet to alpha-helix transformation: application of the switch concept
    Richard Mimna
    Institute of Chemical Sciences and Engineering, Eidgenössische Technische Hochschule Lausanne, 1015 Lausanne, Switzerland
    Angew Chem Int Ed Engl 46:2681-4. 2007
  21. ncbi request reprint Dopamine affects the stability, hydration, and packing of protofibrils and fibrils of the wild type and variants of alpha-synuclein
    Cristian Follmer
    Instituto de Bioquimica Medica, Programa de Biologia Estrutural, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941 590, Brazil
    Biochemistry 46:472-82. 2007
    ..These results suggest that strategies aimed at breaking and/or clearing these aggregates is promising in alleviating the symptoms of PD...
  22. pmc Dissociation of amyloid fibrils of alpha-synuclein and transthyretin by pressure reveals their reversible nature and the formation of water-excluded cavities
    Debora Foguel
    Departamento de Bioquimica Medica, Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941 590, Brazil
    Proc Natl Acad Sci U S A 100:9831-6. 2003
    ..Finally, the HHP-induced formation of fibrils from TTR is relatively fast (approximately 60 min), a quality that allows screening of antiamyloidogenic drugs...
  23. ncbi request reprint Rescuing defective vesicular trafficking protects against alpha-synuclein toxicity in cellular and animal models of Parkinson's disease
    Hilal A Lashuel
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Station 15, CH 1015 Lausanne, Switzerland
    ACS Chem Biol 1:420-4. 2006
    ..Overexpression of proteins that are known to enhance ER-to-Golgi transport rescue defective trafficking in yeast, worm, fly, and cellular models of PD...
  24. ncbi request reprint Abeta protofibrils possess a stable core structure resistant to hydrogen exchange
    Indu Kheterpal
    Graduate School of Medicine, University of Tennessee, 1924 Alcoa Highway, Knoxville, Tennessee 37920, USA
    Biochemistry 42:14092-8. 2003
    ..These and other data are interpreted and discussed in terms of the role of protofibrils in fibril assembly and in disease...
  25. ncbi request reprint Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-beta
    Masayuki Morikawa
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63130, USA
    Neurobiol Dis 19:66-76. 2005
    ..These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS...
  26. ncbi request reprint Amyloid fibril formation by macrophage migration inhibitory factor
    Hilal A Lashuel
    Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology EPFL, CH 1015 Lausanne, Switzerland
    Biochem Biophys Res Commun 338:973-80. 2005
    ....
  27. ncbi request reprint From hexamer to amyloid: marginal stability of apolipoprotein SAA2.2 leads to in vitro fibril formation at physiological temperature
    Limin Wang
    Memorial Sloan Kettering Cancer Center, NY 10021, USA
    Amyloid 12:139-48. 2005
    ..2's inability to cause amyloidosis may be related to other factors, such as the stabilization of hexameric SAA2.2 (possibly through ligand binding), and/or the slow kinetics of aberrant misfolding and self-assembly...
  28. ncbi request reprint Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors
    Vibha B Oza
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 265, La Jolla, California 92037, USA
    J Med Chem 45:321-32. 2002
    ..High-resolution X-ray crystal structures of four of the active compounds bound to TTR were obtained. These demonstrate the significant flexibility with which TTR can accommodate ligands within its two binding sites...