Hilal A Lashuel

Summary

Country: Switzerland

Publications

  1. 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
  2. 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
  3. pmc Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket
    Farah El-Turk
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Department of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland
    PLoS ONE 7:e45024. 2012
  4. doi request reprint One-pot total chemical synthesis of human α-synuclein
    Bruno Fauvet
    Ecole Polytechnique Federale de Lausanne EPFL, Station 19, CH 1015 Lausanne, Switzerland
    Chem Commun (Camb) 49:9254-6. 2013
  5. pmc Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model
    Preeti J Khandelwal
    Department of Neuroscience, Georgetown University Medical Center, Washington D, C, U, S, A, 20007
    Mol Neurodegener 5:47. 2010
  6. 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
  7. 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
  8. pmc The conformational flexibility of the carboxy terminal residues 105-114 is a key modulator of the catalytic activity and stability of macrophage migration inhibitory factor
    Farah El-Turk
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Biochemistry 47:10740-56. 2008
  9. pmc Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions
    Katerina E Paleologou
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, EPFL, Lausanne, Switzerland
    J Neurosci 30:3184-98. 2010
  10. pmc A new class of isothiocyanate-based irreversible inhibitors of macrophage migration inhibitory factor
    Hajer Ouertatani-Sakouhi
    Laboratory of Molecular Neurobiology and Functional Neuroproteomics, Brain Mind Institute and Institute of Biotechnology and Bioengineering, Ecole Polytechnique Federale de Lausanne EPFL, CH 1015 Lausanne, Switzerland
    Biochemistry 48:9858-70. 2009

Collaborators

Detail Information

Publications63

  1. 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
    ....
  2. 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...
  3. pmc Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket
    Farah El-Turk
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Department of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland
    PLoS ONE 7:e45024. 2012
    ..Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state...
  4. doi request reprint One-pot total chemical synthesis of human α-synuclein
    Bruno Fauvet
    Ecole Polytechnique Federale de Lausanne EPFL, Station 19, CH 1015 Lausanne, Switzerland
    Chem Commun (Camb) 49:9254-6. 2013
    ..We herein describe a one-pot total chemical synthesis that should enable site-specific introduction of single or multiple PTMs or small molecule probes essentially at any site within the protein. ..
  5. pmc Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model
    Preeti J Khandelwal
    Department of Neuroscience, Georgetown University Medical Center, Washington D, C, U, S, A, 20007
    Mol Neurodegener 5:47. 2010
    ..Parkin mutations result in loss of parkin E3-ubiquitin ligase activity and cause autosomal recessive early onset parkinsonism...
  6. 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...
  7. 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
    ....
  8. pmc The conformational flexibility of the carboxy terminal residues 105-114 is a key modulator of the catalytic activity and stability of macrophage migration inhibitory factor
    Farah El-Turk
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Biochemistry 47:10740-56. 2008
    ..Our results suggest that targeting the C-terminal region could provide new strategies for allosteric modulation of MIF enzymatic activity and the development of novel inhibitors of MIF tautomerase activity...
  9. pmc Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions
    Katerina E Paleologou
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, EPFL, Lausanne, Switzerland
    J Neurosci 30:3184-98. 2010
    ..Together, our findings provide novel mechanistic insight into the role of phosphorylation at S87 and S129 in the pathogenesis of synucleinopathies and potential roles of phosphorylation in alpha-syn normal biology...
  10. pmc A new class of isothiocyanate-based irreversible inhibitors of macrophage migration inhibitory factor
    Hajer Ouertatani-Sakouhi
    Laboratory of Molecular Neurobiology and Functional Neuroproteomics, Brain Mind Institute and Institute of Biotechnology and Bioengineering, Ecole Polytechnique Federale de Lausanne EPFL, CH 1015 Lausanne, Switzerland
    Biochemistry 48:9858-70. 2009
    ..Together, these findings highlight the role of tertiary structure in modulating the biochemical and biological activities of MIF and present new opportunities for modulating MIF biological activities in vivo...
  11. pmc Characterization of semisynthetic and naturally Nα-acetylated α-synuclein in vitro and in intact cells: implications for aggregation and cellular properties of α-synuclein
    Bruno Fauvet
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Station 19, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 287:28243-62. 2012
    ....
  12. pmc Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action
    Hajer Ouertatani-Sakouhi
    Laboratory of Molecular Neurobiology and Functional Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne EPFL, CH 1015 Lausanne, Switzerland
    J Biol Chem 285:26581-98. 2010
    ....
  13. pmc Phosphorylation of synucleins by members of the Polo-like kinase family
    Martial K Mbefo
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 285:2807-22. 2010
    ....
  14. doi request reprint Switch-peptides: design and characterization of controllable super-amyloid-forming host-guest peptides as tools for identifying anti-amyloid agents
    Marie Stéphanie Camus
    Institute of Chemical Sciences and Engineering ISIC, Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Chembiochem 9:2104-12. 2008
    ....
  15. pmc Phosphorylation of α-Synuclein at Y125 and S129 alters its metal binding properties: implications for understanding the role of α-Synuclein in the pathogenesis of Parkinson's Disease and related disorders
    Yu Lu
    Laboratoire d Electrochimie Physique et Analytique, Station 6, Ecole Polytechnique Federale de Lausane, CH 1015 Lausanne, Switzerland
    ACS Chem Neurosci 2:667-75. 2011
    ....
  16. pmc α-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer
    Bruno Fauvet
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Station 19, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 287:15345-64. 2012
    ..These results do not rule out the possibility that α-syn becomes structured upon interaction with other proteins and/or biological membranes...
  17. doi request reprint Kinetic-based high-throughput screening assay to discover novel classes of macrophage migration inhibitory factor inhibitors
    Hajer Ouertatani-Sakouhi
    Laboratory of Molecular Neurobiology and Functional Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    J Biomol Screen 15:347-58. 2010
    ..Using this assay, they screened 80,000 small molecules and identified and validated 13 novel inhibitors of MIF catalytic activity. These small molecules demonstrated inhibition constant (K(i,app)) values ranging from 0.5 to 13 microM...
  18. pmc Abeta42 neurotoxicity is mediated by ongoing nucleated polymerization process rather than by discrete Abeta42 species
    Asad Jan
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 286:8585-96. 2011
    ....
  19. doi request reprint Role of post-translational modifications in modulating the structure, function and toxicity of alpha-synuclein: implications for Parkinson's disease pathogenesis and therapies
    Abid Oueslati
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, The Ecole Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland
    Prog Brain Res 183:115-45. 2010
    ..Furthermore, the identification of the natural enzymes involved in regulating the post-translational modifications of alpha-synuclein will yield novel and more tractable therapeutic targets to treat PD and related synucleinopathies...
  20. doi request reprint Structure and function of the molecular chaperone Hsp104 from yeast
    Valerie Grimminger-Marquardt
    Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology Lausanne EPFL, FSV BMI AI 2137 1, Station 15, CH 1015 Lausanne, Switzerland
    Biopolymers 93:252-76. 2010
    ....
  21. doi request reprint Novel mechanistic insight into the molecular basis of amyloid polymorphism and secondary nucleation during amyloid formation
    Jae Sun Jeong
    Laboratory of Physics of Living Matter, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Mol Biol 425:1765-81. 2013
    ..g., diffuse versus amyloid plaques), and of the structural basis of Aβ toxicity...
  22. doi request reprint Establishing the links between Aβ aggregation and cytotoxicity in vitro using biophysical approaches
    Asad Jan
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    Methods Mol Biol 849:227-43. 2012
    ..The individual assays are well-established, commonly used, rely on easily accessible materials and can be performed within 24 h...
  23. doi request reprint Mimicking phosphorylation at serine 87 inhibits the aggregation of human α-synuclein and protects against its toxicity in a rat model of Parkinson's disease
    Abid Oueslati
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Neurosci 32:1536-44. 2012
    ....
  24. pmc Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity
    Saviana Di Giovanni
    Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology Lausanne, SV BMI LMNN AI2351, CH 1015 Lausanne, Switzerland
    J Biol Chem 285:14941-54. 2010
    ..Their inhibitory properties, mode of action, and structural properties suggest that they constitute promising lead compounds for further optimization...
  25. pmc Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo
    Abid Oueslati
    Laboratory of Molecular and Chemical Biology of Neurodegeneration and Neurodegenerative Disease Laboratory, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Proc Natl Acad Sci U S A 110:E3945-54. 2013
    ..Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of α-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies. ..
  26. doi request reprint Chemical strategies for controlling protein folding and elucidating the molecular mechanisms of amyloid formation and toxicity
    SARA BUTTERFIELD
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Mol Biol 421:204-36. 2012
    ....
  27. pmc The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity
    Asad Jan
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 283:28176-89. 2008
    ....
  28. pmc Dissecting the mechanisms of tissue transglutaminase-induced cross-linking of alpha-synuclein: implications for the pathogenesis of Parkinson disease
    Adrien W Schmid
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    J Biol Chem 284:13128-42. 2009
    ....
  29. doi request reprint Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability
    Igor Allaman
    Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    J Neurosci 30:3326-38. 2010
    ..This set of observations indicates that Abeta aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability...
  30. pmc c-Abl phosphorylates α-synuclein and regulates its degradation: implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson's disease
    Anne Laure Mahul-Mellier
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute
    Hum Mol Genet 23:2858-79. 2014
    ..Together, these data suggest that changes in c-Abl expression, activation and/or c-Abl-mediated phosphorylation of Y39 play a role in regulating α-syn clearance and contribute to the pathogenesis of PD. ..
  31. doi request reprint One-pot semisynthesis of exon 1 of the Huntingtin protein: new tools for elucidating the role of posttranslational modifications in the pathogenesis of Huntington's disease
    Annalisa Ansaloni
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne Switzerland
    Angew Chem Int Ed Engl 53:1928-33. 2014
    ..The ability to produce wt or site-specifically modified tag-free Httex1 should facilitate determining its structure and the role of N-terminal PTMs in regulating the functions of Htt in health and disease. ..
  32. doi request reprint Amyloidogenic protein-membrane interactions: mechanistic insight from model systems
    Sara M Butterfield
    Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology Lausanne EPFL, SV BMI LMNN AI2351, 1015 Lausanne, Switzerland
    Angew Chem Int Ed Engl 49:5628-54. 2010
    ..Recent studies with artificial model membranes have highlighted the striking resemblance of the mechanisms of membrane permeabilization of amyloid-forming proteins to those of pore-forming toxins and antimicrobial peptides...
  33. doi request reprint The many faces of α-synuclein: from structure and toxicity to therapeutic target
    Hilal A Lashuel
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Nat Rev Neurosci 14:38-48. 2013
    ..Understanding the nature of the various α-syn structures, how they are formed and their relative contributions to α-syn-mediated toxicity may inform future studies aiming to develop therapeutic prevention and intervention...
  34. doi request reprint An integrative in silico methodology for the identification of modulators of macrophage migration inhibitory factor (MIF) tautomerase activity
    Farah El Turk
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne EPFL, CH 1015 Lausanne, Switzerland
    Bioorg Med Chem 18:5425-40. 2010
    ..The chemical diversity and mode of action of these compounds suggest that they could be used as molecular probes to elucidate the functions and biology of MIF and as lead candidates in drug developments of anti-MIF drugs...
  35. ncbi request reprint Hsp104 targets multiple intermediates on the amyloid pathway and suppresses the seeding capacity of Abeta fibrils and protofibrils
    Muriel Arimon
    Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology Lausanne EPFL, FSV BMI AI 2137 1, Station 15, CH 1015 Lausanne, Switzerland
    J Mol Biol 384:1157-73. 2008
    ..Together, these findings suggest that the strong inhibition of Abeta fibrillization by Hsp104 is mediated by its ability to act at different stages and target multiple intermediates on the pathway to amyloid formation...
  36. ncbi request reprint Preparation and characterization of toxic Abeta aggregates for structural and functional studies in Alzheimer's disease research
    Asad Jan
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    Nat Protoc 5:1186-209. 2010
    ..The procedures described can be performed in as little as 1 day, or may take longer, depending on the exact toxicity assays used...
  37. pmc Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein
    Katerina E Paleologou
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 283:16895-905. 2008
    ....
  38. pmc Alpha-synuclein post-translational modifications as potential biomarkers for Parkinson disease and other synucleinopathies
    Adrien W Schmid
    Proteomics Core Facility, School of Life Sciences, Station 19, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Mol Cell Proteomics 12:3543-58. 2013
    ....
  39. pmc Elucidating the role of C-terminal post-translational modifications using protein semisynthesis strategies: α-synuclein phosphorylation at tyrosine 125
    Mirva Hejjaoui
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne EPFL, CH 1015 Lausanne, Switzerland
    J Am Chem Soc 134:5196-210. 2012
    ....
  40. pmc Discovery and structure activity relationship of small molecule inhibitors of toxic β-amyloid-42 fibril formation
    Heiko Kroth
    AC Immune SA, PSE Building B, Swiss Federal Institute of Technology Lausanne EPFL, CH 1015 Lausanne, Switzerland
    J Biol Chem 287:34786-800. 2012
    ..Using structure activity relationship data from the in vitro assays, we identified compounds capable of preventing pathological self-assembly of Aβ42 leading to decreased cell toxicity...
  41. doi request reprint Discovery of a novel aggregation domain in the huntingtin protein: implications for the mechanisms of Htt aggregation and toxicity
    Zhe Ming Wang
    Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Switzerland
    Angew Chem Int Ed Engl 52:562-7. 2013
    ..Potential cross-talk between this domain and the polyQ region may play a central role in regulating the aggregation and toxicity of Htt-N-terminal fragments...
  42. 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
    ....
  43. 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
    ....
  44. 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...
  45. 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...
  46. 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
    ....
  47. 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...
  48. 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...
  49. 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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
  55. 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...
  56. 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...
  57. 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...
  58. 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...
  59. 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...
  60. 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
    ....
  61. 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...
  62. 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...
  63. 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...