Characterising protein oligomers and their role in neurodegenerative disease in humans

Información del proyecto

Oligomers

Identificador del acuerdo de subvención: 669237

DOI

10.3030/669237

Proyecto cerrado

Fecha de la firma de la CE 25 Agosto 2015

Fecha de inicio 1 Septiembre 2015

Fecha de finalización 31 Agosto 2021

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 2 499 551,00

Aportación de la UE

€ 2 499 551,00

Coordinado por

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

CORDIS proporciona enlaces a los documentos públicos y las publicaciones de los proyectos de los programas marco HORIZONTE.

Los enlaces a los documentos y las publicaciones de los proyectos del Séptimo Programa Marco, así como los enlaces a algunos tipos de resultados específicos, como conjuntos de datos y «software», se obtienen dinámicamente de OpenAIRE .

Publicaciones

Peer reviewed articles (25)

Filamentous Aggregates Are Fragmented by the Proteasome Holoenzyme

Autores: Rachel Cliffe, Jason C. Sang, Franziska Kundel, Daniel Finley, David Klenerman, Yu Ye
Publicado en: Cell Reports, Edición 26/8, 2019, Página(s) 2140-2149.e3, ISSN 2211-1247
Editor: Cell Press
DOI: 10.1016/j.celrep.2019.01.096

Imaging individual protein aggregates to follow aggregation and determine the role of aggregates in neurodegenerative disease

Autores: Suman De, David Klenerman
Publicado en: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Edición 1867/10, 2019, Página(s) 870-878, ISSN 1570-9639
Editor: Elsevier BV
DOI: 10.1016/j.bbapap.2018.12.010

Super-resolution imaging reveals α-synuclein seeded aggregation in SH-SY5Y cells

Autores: Jason C. Sang, Eric Hidari, Georg Meisl, Rohan T. Ranasinghe, Maria Grazia Spillantini, David Klenerman
Publicado en: Communications Biology, Edición 4/1, 2021, ISSN 2399-3642
Editor: Communication Biology
DOI: 10.1038/s42003-021-02126-w

In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease

Autores: Georg Meisl , Eric Hidari , Kieren Allinson , Timothy Rittman , Sarah L DeVos , Justin S Sanchez , Catherine K Xu , Karen E Duff , Keith A Johnson , James B Rowe , Bradley T Hyman, Tuomas P J Knowles , David Klenerman
Publicado en: Science Advances, 2021, ISSN 2375-2548
Editor: AAAS
DOI: 10.1126/sciadv.abh1448

Soluble amyloid beta-containing aggregates are present throughout the brain at early stages of Alzheimer’s disease

Autores: Dimitrios I Sideris, John S H Danial, Derya Emin, Francesco S Ruggeri, Zengjie Xia, Yu P Zhang, Evgeniia Lobanova, Helen Dakin, Suman De, Alyssa Miller, Jason C Sang, Tuomas P J Knowles, Michele Vendruscolo, Graham Fraser, Damian Crowther, David Klenerman
Publicado en: Brain Communications, Edición 3/3, 2021, ISSN 2632-1297
Editor: Oxford University Press
DOI: 10.1093/braincomms/fcab147

Analysis of α-synuclein species enriched from cerebral cortex of humans with sporadic dementia with Lewy bodies

Autores: John B Sanderson, Suman De, Haiyang Jiang, Matteo Rovere, Ming Jin, Ludovica Zaccagnini, Aurelia Hays Watson, Laura De Boni, Valentina N Lagomarsino, Tracy L Young-Pearse, Xinyue Liu, Thomas C Pochapsky, Bradley T Hyman, Dennis W Dickson, David Klenerman, Dennis J Selkoe, Tim Bartels
Publicado en: Brain Communications, Edición 2/1, 2020, ISSN 2632-1297
Editor: Oxford University Press
DOI: 10.1093/braincomms/fcaa010

Optical structural analysis of individual α-synuclein oligomers

Autores: Juan Alberto Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi, Christopher M. Dobson, David Klenerman, Steven Lee
Publicado en: Angewandte Chemie International Edition, Edición 12, 2018, ISSN 1433-7851
Editor: John Wiley & Sons Ltd.
DOI: 10.1002/anie.201710779

Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity

Autores: Franziska Kundel, Suman De, Patrick Flagmeier, Mathew H. Horrocks, Magnus Kjaergaard, Sarah L. Shammas, Sophie E. Jackson, Christopher M. Dobson, David Klenerman
Publicado en: ACS Chemical Biology, Edición 12, 2018, ISSN 1554-8929
Editor: American Chemical Society
DOI: 10.1021/acschembio.7b01039

Nanobodies raised against monomeric ɑ-synuclein inhibit fibril formation and destabilize toxic oligomeric species

Autores: Marija Iljina, Liu Hong, Mathew H. Horrocks, Marthe H. Ludtmann, Minee L. Choi, Craig D. Hughes, Francesco S. Ruggeri, Tim Guilliams, Alexander K. Buell, Ji-Eun Lee, Sonia Gandhi, Steven F. Lee, Clare E. Bryant, Michele Vendruscolo, Tuomas P. J. Knowles, Christopher M. Dobson, Erwin De Genst, David Klenerman
Publicado en: BMC Biology, Edición 15/1, 2017, ISSN 1741-7007
Editor: BioMed Central
DOI: 10.1186/s12915-017-0390-6

Ultrasensitive Measurement of Ca 2+ Influx into Lipid Vesicles Induced by Protein Aggregates

Autores: Patrick Flagmeier, Suman De, David C. Wirthensohn, Steven F. Lee, Cécile Vincke, Serge Muyldermans, Tuomas P. J. Knowles, Sonia Gandhi, Christopher M. Dobson, David Klenerman
Publicado en: Angewandte Chemie International Edition, Edición 56/27, 2017, Página(s) 7750-7754, ISSN 1433-7851
Editor: John Wiley & Sons Ltd.
DOI: 10.1002/anie.201700966

Inhibiting the Ca 2+ Influx Induced by Human CSF

Autores: Anna Drews, Suman De, Patrick Flagmeier, David C. Wirthensohn, Wei-Hsin Chen, Daniel R. Whiten, Margarida Rodrigues, Cécile Vincke, Serge Muyldermans, Ross W. Paterson, Catherine F. Slattery, Nick C. Fox, Jonathan M. Schott, Henrik Zetterberg, Christopher M. Dobson, Sonia Gandhi, David Klenerman
Publicado en: Cell Reports, Edición 21/11, 2017, Página(s) 3310-3316, ISSN 2211-1247
Editor: Cell Press
DOI: 10.1016/j.celrep.2017.11.057

Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic α-Synuclein Oligomers

Autores: Daniel R. Whiten, Dezerae Cox, Mathew H. Horrocks, Christopher G. Taylor, Suman De, Patrick Flagmeier, Laura Tosatto, Janet R. Kumita, Heath Ecroyd, Christopher M. Dobson, David Klenerman, Mark R. Wilson
Publicado en: Cell Reports, Edición 23/12, 2018, Página(s) 3492-3500, ISSN 2211-1247
Editor: Cell Press
DOI: 10.1016/j.celrep.2018.05.074

Nanoscopic characterization of individual endogenous protein aggregates in human neuronal cells

Autores: Mathew Horrocks, Daniel R Whiten, Yukun Zuo, Laura Calo, Minee-Liane Choi, Suman De, Patrick Flagmeier, David C Wirthensohn, Franziska Kundel, Steven F Lee, Christopher Dobson, Sonia Gandhi, Maria Spillantini, David Klenerman, Rohan T Ranasinghe, Santiago E Sanchez, Dilan Athauda
Publicado en: ChemBioChem, 2018, ISSN 1439-4227
Editor: John Wiley & Sons Ltd.
DOI: 10.1002/cbic.201800209

Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading

Autores: Kundel, F.; Hong, L.; Falcon, B.; McEwan, W. A.; Michaels, T. C. T.; Meisl, G.; Esteras, N.; Abramov, A. Y.; Knowles, T. J. P.; Goedert, M.; Klenerman, D.
Publicado en: ACS Chemical Neuroscience (2018), 2018, Página(s) 1276–1282, ISSN 1948-7193
Editor: American Chemical Society
DOI: 10.17863/CAM.25419

Extrinsic Amyloid-Binding Dyes for Detection of Individual Protein Aggregates in Solution

Autores: Christopher G. Taylor, Georg Meisl, Mathew H. Horrocks, Henrik Zetterberg, Tuomas P. J. Knowles, David Klenerman
Publicado en: Analytical Chemistry, Edición 90/17, 2018, Página(s) 10385-10393, ISSN 0003-2700
Editor: American Chemical Society
DOI: 10.1021/acs.analchem.8b02226

Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells

Autores: Anna Drews, Jennie Flint, Nadia Shivji, Peter Jönsson, David Wirthensohn, Erwin De Genst, Cécile Vincke, Serge Muyldermans, Chris Dobson, David Klenerman
Publicado en: Scientific Reports, Edición 6/1, 2016, ISSN 2045-2322
Editor: Nature Publishing Group
DOI: 10.1038/srep31910

Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms

Autores: Suman De, David C. Wirthensohn, Patrick Flagmeier, Craig Hughes, Francesco A. Aprile, Francesco S. Ruggeri, Daniel R. Whiten, Derya Emin, Zengjie Xia, Juan A. Varela, Pietro Sormanni, Franziska Kundel, Tuomas P. J. Knowles, Christopher M. Dobson, Clare Bryant, Michele Vendruscolo, David Klenerman
Publicado en: Nature Communications, Edición 10/1, 2019, ISSN 2041-1723
Editor: Nature Publishing Group
DOI: 10.1038/s41467-019-09477-3

Soluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer’s disease progression

Autores: Suman De, Daniel R. Whiten, Francesco S. Ruggeri, Craig Hughes, Margarida Rodrigues, Dimitrios I. Sideris, Christopher G. Taylor, Francesco A. Aprile, Serge Muyldermans, Tuomas P. J. Knowles, Michele Vendruscolo, Clare Bryant, Kaj Blennow, Ingmar Skoog, Silke Kern, Henrik Zetterberg, David Klenerman
Publicado en: Acta Neuropathologica Communications, Edición 7/1, 2019, ISSN 2051-5960
Editor: BioMed Central
DOI: 10.1186/s40478-019-0777-4

Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale

Autores: Ji-Eun Lee, Jason C. Sang, Margarida Rodrigues, Alexander R. Carr, Mathew H. Horrocks, Suman De, Marie N. Bongiovanni, Patrick Flagmeier, Christopher M. Dobson, David J. Wales, Steven F. Lee, David Klenerman
Publicado en: Nano Letters, Edición 18/12, 2018, Página(s) 7494-7501, ISSN 1530-6984
Editor: American Chemical Society
DOI: 10.1021/acs.nanolett.8b02916

Picomolar concentrations of oligomeric alpha-synuclein sensitizes TLR4 to play an initiating role in Parkinson’s disease pathogenesis

Autores: Craig D. Hughes, Minee L. Choi, Mina Ryten, Lee Hopkins, Anna Drews, Juan A. Botía, Maria Iljina, Margarida Rodrigues, Sarah A. Gagliano, Sonia Gandhi, Clare Bryant, David Klenerman
Publicado en: Acta Neuropathologica, Edición 137/1, 2019, Página(s) 103-120, ISSN 0001-6322
Editor: Springer Verlag
DOI: 10.1007/s00401-018-1907-y

Beta amyloid aggregates induce sensitised TLR4 signalling causing long-term potentiation deficit and rat neuronal cell death

Autores: Craig Hughes, Minee L. Choi, Jee-Hyun Yi, Seung-Chan Kim, Anna Drews, Peter St. George-Hyslop, Clare Bryant, Sonia Gandhi, Kwangwook Cho, David Klenerman
Publicado en: Communications Biology, Edición 3/1, 2020, ISSN 2399-3642
Editor: Nature research
DOI: 10.1038/s42003-020-0792-9

Quantifying Co-Oligomer Formation by α-Synuclein

Autores: Marija Iljina, Alexander J. Dear, Gonzalo A. Garcia, Suman De, Laura Tosatto, Patrick Flagmeier, Daniel R. Whiten, Thomas C. T. Michaels, Daan Frenkel, Christopher M. Dobson, Tuomas P. J. Knowles, David Klenerman
Publicado en: ACS Nano, Edición 12/11, 2018, Página(s) 10855-10866, ISSN 1936-0851
Editor: American Chemical Society
DOI: 10.1021/acsnano.8b03575

Alpha Synuclein only Forms Fibrils In Vitro when Larger than its Critical Size of 70 Monomers

Autores: Santiago Enrique Sanchez, Daniel R. Whiten, Georg Meisl, Francesco Simone Ruggeri, Eric Hidari, David Klenerman
Publicado en: ChemBioChem, 2021, ISSN 1439-4227
Editor: John Wiley & Sons Ltd.
DOI: 10.1002/cbic.202100285

Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson’s disease

Autores: Evgeniia Lobanova, Daniel Whiten, Francesco S Ruggeri, Chris Taylor, Antonina Kouli, Zengjie Xia, Derya Emin, Yu P Zhang, Jeff Y L Lam, Caroline H Williams-Gray, David Klenerman
Publicado en: Brain, 2021, ISSN 0006-8950
Editor: Oxford University Press
DOI: 10.1093/brain/awab306

Tumour necrosis factor induces increased production of extracellular amyloid-β- and α-synuclein-containing aggregates by human Alzheimer’s disease neurons

Autores: Daniel R Whiten, Philip W Brownjohn, Steven Moore, Suman De, Alessio Strano, Yukun Zuo, Moritz Haneklaus, David Klenerman, Frederick J Livesey
Publicado en: Brain Communications, Edición 2/2, 2020, ISSN 2632-1297
Editor: Oxford University Press
DOI: 10.1093/braincomms/fcaa146