David TeplowSummaryAffiliation: University of California Country: USA Publications
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Publications
Quasielastic light scattering for protein assembly studiesAleksey Lomakin
Department of Physics and Center for Materials Sciences and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
Methods Mol Biol 299:153-74. 2005..We use examples from studies of Abeta fibrillogenesis to illustrate QLS application for understanding the molecular mechanisms of the nucleation and growth of amyloid fibrils...- Preparation of amyloid beta-protein for structural and functional studiesDavid B Teplow
David Geffen School of Medicine at UCLA, Department of Neurology, Los Angeles, California, USA
Methods Enzymol 413:20-33. 2006..This approach produces Abeta solutions that have been used successfully in a variety of in vitro and in vivo experimental systems... - Elucidating amyloid beta-protein folding and assembly: A multidisciplinary approachDavid 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... - Neurotoxic protein oligomers--what you see is not always what you getGal Bitan
Department of Neurology, David Geffen School of Medicine at UCLA, 90095 7334, USA
Amyloid 12:88-95. 2005.... 
Amyloid beta-protein monomer folding: free-energy surfaces reveal alloform-specific differencesMingfeng Yang
Department of Neurology, David Geffen School of Medicine, and Molecular Biology Institute and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
J Mol Biol 384:450-64. 2008..The conformers also provide starting points for simulations of Abeta oligomerization-a process postulated to be the key pathogenetic event in Alzheimer's disease...- Conformational dynamics of amyloid beta-protein assembly probed using intrinsic fluorescenceSamir K Maji
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
Biochemistry 44:13365-76. 2005.... - On the nucleation of amyloid beta-protein monomer foldingNoel D Lazo
Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza (Reed C119A, Los Angeles, CA 90095, USA
Protein Sci 14:1581-96. 2005..Our results suggest that therapeutic approaches targeting the Val24-Lys28 turn or the Abeta(1-42)-specific C-terminal fold may hold promise... - Amino acid position-specific contributions to amyloid beta-protein oligomerizationSamir K Maji
Department of Neurology, UCLA, Los Angeles, California 90095, USA
J Biol Chem 284:23580-91. 2009.... - Effects of familial Alzheimer's disease mutations on the folding nucleation of the amyloid beta-proteinMary Griffin Krone
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106 9510, USA
J Mol Biol 381:221-8. 2008..Our simulations suggest that the mechanisms by which E22 and D23 mutations affect the folding and aggregation of Abeta are fundamentally different... - Effects of grape seed-derived polyphenols on amyloid beta-protein self-assembly and cytotoxicityKenjiro Ono
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California 90095 7334, USA
J Biol Chem 283:32176-87. 2008..These data suggest that MN is worthy of consideration as a therapeutic agent for AD... - Kinetic studies of amyloid beta-protein fibril assembly. Differential effects of alpha-helix stabilizationYoucef Fezoui
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 277:36948-54. 2002..Our results suggest that in vivo, factors that affect helix formation and stability will have significant effects on the kinetics of Abeta fibril formation... - Amyloid beta-protein assembly as a therapeutic target of Alzheimer's diseaseGhiam Yamin
Department of Neurology, David Geffen School of Medicine at UCLA, 635 Charles E Young Drive South Room 445, Los Angeles, California 90095, USA
Curr Pharm Des 14:3231-46. 2008..We also discuss briefly a number of less mature, but intriguing, strategies that have therapeutic potential. Although initial trials of some disease-modifying agents have failed, we argue that substantial cause for optimism exists... - Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assembliesMarina 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... - Amyloid beta protein: Abeta40 inhibits Abeta42 oligomerizationMegan M Murray
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106 950, USA
J Am Chem Soc 131:6316-7. 2009..Abeta40 alone produces such a distribution, whereas Abeta42 alone produces oligomers as large as dodecamers. This indicates that Abeta40 inhibits Abeta42 oligomerization... 
Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathyJustin Zaghi
Department of Orthopaedic Surgery, UCLA Orthopaedic Hospital Research Center, Los Angeles, CA 90095 7358, USA
Acta Neuropathol 117:111-24. 2009..In conclusion, in patients with AD, macrophages appear to shuttle Abeta from neurons to vessels where their apoptosis may release fibrillar Abeta, contributing to cerebral amyloid angiopathy...- Amyloid beta-protein monomer structure: a computational and experimental studyAndrij 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... - Amyloid beta-protein: experiment and theory on the 21-30 fragmentMegan M Murray
Department of Chemistry, University of California, Santa Barbara, California 93106, USA
J Phys Chem B 113:6041-6. 2009.... - Structure-neurotoxicity relationships of amyloid beta-protein oligomersKenjiro Ono
Department of Neurology, David Geffen School of Medicine, and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 106:14745-50. 2009..The structure-activity correlations reported here significantly extend our understanding of the conformational dynamics, structure, and relative toxicity of pure Abeta oligomers of specific order... - Amyloid beta-protein: monomer structure and early aggregation states of Abeta42 and its Pro19 alloformSummer 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]... - A molecular switch in amyloid assembly: Met35 and amyloid beta-protein oligomerizationGal 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... - A direct interaction between transforming growth factor (TGF)-betas and amyloid-beta protein affects fibrillogenesis in a TGF-beta receptor-independent mannerDarrell D Mousseau
Cell Signaling Group, Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon S7N 5E4, Canada
J Biol Chem 278:38715-22. 2003..These data support a critical etiological role for this mechanism in neuropathological amyloidoses... - Kinetics of amyloid beta-protein degradation determined by novel fluorescence- and fluorescence polarization-based assaysMalcolm A Leissring
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
J Biol Chem 278:37314-20. 2003..The use of these assays should yield additional new insights into the biology of Abeta-degrading proteases and facilitate the identification of activators and inhibitors of such enzymes... - Elucidation of primary structure elements controlling early amyloid beta-protein oligomerizationGal 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... - Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathwaysGal 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... - Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscansUvidelio F Castillo
Dept of Plant Sciences, Montana State University, Bozeman, MT 59717, USA
Microbiology 148:2675-85. 2002..5+/-0.07 ng x ml(-1). This report also describes the potential of the munumbicins in medicine and agriculture... - A non-amyloidogenic function of BACE-2 in the secretory pathwayRegina Fluhrer
Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-University, Munich, Germany
J Neurochem 81:1011-20. 2002..These data indicate that the distinct specificities of BACE-1 and BACE-2 in their cleavage of betaAPP differentially affect the generation of Abeta... - Structure determination of micelle-like intermediates in amyloid beta -protein fibril assembly by using small angle neutron scatteringWinnie Yong
Department of Physics, Center for Materials Science and Engineering, and Materials Processing Center, Massachusetts Institute of Technology, Cambridge, MA 02139 4307, USA
Proc Natl Acad Sci U S A 99:150-4. 2002..The concentration independence of the length of the cylindrical aggregate indicates the presence of an internal nonrepetitive structure that spans the entire length of the Abeta assembly... - Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's diseaseJun Wang
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
J Neurosci 28:6388-92. 2008..Our study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat AD... - Familial Alzheimer's disease mutations alter the stability of the amyloid beta-protein monomer folding nucleusMarianne A Grant
Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 104:16522-7. 2007..The implications of these findings for understanding Abeta monomer folding and disease causation are discussed... - Determination of Peptide oligomerization state using rapid photochemical crosslinkingSabrina 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... - Preparation of aggregate-free, low molecular weight amyloid-beta for assembly and toxicity assaysGal 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... - Solvent and mutation effects on the nucleation of amyloid beta-protein foldingLuis Cruz
Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 102:18258-63. 2005.... - Folding events in the 21-30 region of amyloid beta-protein (Abeta) studied in silicoJose M Borreguero
Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 102:6015-20. 2005..Substitutions may alter the frequency of Glu-22 or Asp-23 involvement in contact formation and affect the stability of the folding nucleus formed in the Abeta(21-30) region... - Quasielastic light scattering study of amyloid beta-protein fibril formationAleksey Lomakin
Department of Physics and Center for Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Protein Pept Lett 13:247-54. 2006..We illustrate practical applications of QLS with examples from studies of fibril formation of the amyloid beta-protein... - Structure of the 21-30 fragment of amyloid beta-proteinAndrij Baumketner
Department of Chemistry and Biochemistry, University of California at Santa Barbara, California 93106, USA
Protein Sci 15:1239-47. 2006..The persistence of structure in the denatured state may account for the resistance of this peptide to protease degradation and aggregation, even at elevated temperatures... - Rapid photochemical cross-linking--a new tool for studies of metastable, amyloidogenic protein assembliesGal 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... - Computer simulations of Alzheimer's amyloid beta-protein folding and assemblyBrigita Urbanc
Center for Polymer Studies, Department of Physics, Boston University, Boston, MA 02215, USA
Curr Alzheimer Res 3:493-504. 2006.... - Apical sorting of beta-secretase limits amyloid beta-peptide productionAnja Capell
Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Schillerstrasse 44, Ludwig-Maximilians-University, Munich 80336, Germany
J Biol Chem 277:5637-43. 2002..These data demonstrate that Abeta production is limited in polarized cells by differential targeting of BACE and its substrate betaAPP. Moreover, our findings suggest that betaAPP may not be a major physiological substrate of BACE...
Research Grants
- Structural and Kinetic Analysis of ABeta FibrillogenesisDavid Teplow; Fiscal Year: 2005..Aim 2. To determine the topological organization of amino acids during ABeta folding and assembly. Aim 3. To determine the effects of novel AD- and CAA-associated amino acid substitutions on ABeta folding and assembly. ..
- 3D Structure of Amyloid beta-Protein AssembliesDavid Teplow; Fiscal Year: 2006..Aim ID. To identify interacting amino acids in AB fibrils. Aim 2. To construct an experimentally-based, dynamic, three-dimensional model of AB fibril assembly. ..
- Formation and Function of Prefibrillar Amyloid Beta AssembliesDavid Teplow; Fiscal Year: 2007..Aim 3. To determine the structure and mechanism of action of oligomeric Abeta fibrillogenesis inhibitors. Aim 4. To determine the biological activity of early intermediates. ..
- PROCISE cLC Sequencing System 2 Cart w/PCDavid Teplow; Fiscal Year: 2004..abstract_text> ..
- STRUCTURAL/KINETIC ANALYSIS OF ABETA FIBRILLOGENESISDavid Teplow; Fiscal Year: 2001....
- Structural Biology of Amyloid Beta-ProteinDavid B Teplow; Fiscal Year: 2010..The project also will be of relevance to Parkinsons, Huntingtons, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, the prionoses, and other neurodegenerative diseases of aging. ..