Characterising protein oligomers and their role in neurodegenerative disease in humans

Project Information

Oligomers

Grant agreement ID: 669237

DOI

10.3030/669237

Project closed

EC signature date 25 August 2015

Start date 1 September 2015

End date 31 August 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 499 551,00

EU contribution

€ 2 499 551,00

Coordinated by

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

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Publications

Peer reviewed articles (25)

Filamentous Aggregates Are Fragmented by the Proteasome Holoenzyme

Author(s): Rachel Cliffe, Jason C. Sang, Franziska Kundel, Daniel Finley, David Klenerman, Yu Ye
Published in: Cell Reports, Issue 26/8, 2019, Page(s) 2140-2149.e3, ISSN 2211-1247
Publisher: 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

Author(s): Suman De, David Klenerman
Published in: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Issue 1867/10, 2019, Page(s) 870-878, ISSN 1570-9639
Publisher: Elsevier BV
DOI: 10.1016/j.bbapap.2018.12.010

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

Author(s): Jason C. Sang, Eric Hidari, Georg Meisl, Rohan T. Ranasinghe, Maria Grazia Spillantini, David Klenerman
Published in: Communications Biology, Issue 4/1, 2021, ISSN 2399-3642
Publisher: Communication Biology
DOI: 10.1038/s42003-021-02126-w

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

Author(s): 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
Published in: Science Advances, 2021, ISSN 2375-2548
Publisher: AAAS
DOI: 10.1126/sciadv.abh1448

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

Author(s): 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
Published in: Brain Communications, Issue 3/3, 2021, ISSN 2632-1297
Publisher: 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

Author(s): 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
Published in: Brain Communications, Issue 2/1, 2020, ISSN 2632-1297
Publisher: Oxford University Press
DOI: 10.1093/braincomms/fcaa010

Optical structural analysis of individual α-synuclein oligomers

Author(s): Juan Alberto Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi, Christopher M. Dobson, David Klenerman, Steven Lee
Published in: Angewandte Chemie International Edition, Issue 12, 2018, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.201710779

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

Author(s): Franziska Kundel, Suman De, Patrick Flagmeier, Mathew H. Horrocks, Magnus Kjaergaard, Sarah L. Shammas, Sophie E. Jackson, Christopher M. Dobson, David Klenerman
Published in: ACS Chemical Biology, Issue 12, 2018, ISSN 1554-8929
Publisher: American Chemical Society
DOI: 10.1021/acschembio.7b01039

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

Author(s): 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
Published in: BMC Biology, Issue 15/1, 2017, ISSN 1741-7007
Publisher: BioMed Central
DOI: 10.1186/s12915-017-0390-6

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

Author(s): 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
Published in: Angewandte Chemie International Edition, Issue 56/27, 2017, Page(s) 7750-7754, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.201700966

Inhibiting the Ca 2+ Influx Induced by Human CSF

Author(s): 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
Published in: Cell Reports, Issue 21/11, 2017, Page(s) 3310-3316, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2017.11.057

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

Author(s): 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
Published in: Cell Reports, Issue 23/12, 2018, Page(s) 3492-3500, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2018.05.074

Nanoscopic characterization of individual endogenous protein aggregates in human neuronal cells

Author(s): 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
Published in: ChemBioChem, 2018, ISSN 1439-4227
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/cbic.201800209

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

Author(s): 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.
Published in: ACS Chemical Neuroscience (2018), 2018, Page(s) 1276–1282, ISSN 1948-7193
Publisher: American Chemical Society
DOI: 10.17863/CAM.25419

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

Author(s): Christopher G. Taylor, Georg Meisl, Mathew H. Horrocks, Henrik Zetterberg, Tuomas P. J. Knowles, David Klenerman
Published in: Analytical Chemistry, Issue 90/17, 2018, Page(s) 10385-10393, ISSN 0003-2700
Publisher: 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

Author(s): Anna Drews, Jennie Flint, Nadia Shivji, Peter Jönsson, David Wirthensohn, Erwin De Genst, Cécile Vincke, Serge Muyldermans, Chris Dobson, David Klenerman
Published in: Scientific Reports, Issue 6/1, 2016, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/srep31910

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

Author(s): 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
Published in: Nature Communications, Issue 10/1, 2019, ISSN 2041-1723
Publisher: 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

Author(s): 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
Published in: Acta Neuropathologica Communications, Issue 7/1, 2019, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-019-0777-4

Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale

Author(s): 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
Published in: Nano Letters, Issue 18/12, 2018, Page(s) 7494-7501, ISSN 1530-6984
Publisher: 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

Author(s): 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
Published in: Acta Neuropathologica, Issue 137/1, 2019, Page(s) 103-120, ISSN 0001-6322
Publisher: 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

Author(s): 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
Published in: Communications Biology, Issue 3/1, 2020, ISSN 2399-3642
Publisher: Nature research
DOI: 10.1038/s42003-020-0792-9

Quantifying Co-Oligomer Formation by α-Synuclein

Author(s): 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
Published in: ACS Nano, Issue 12/11, 2018, Page(s) 10855-10866, ISSN 1936-0851
Publisher: American Chemical Society
DOI: 10.1021/acsnano.8b03575

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

Author(s): Santiago Enrique Sanchez, Daniel R. Whiten, Georg Meisl, Francesco Simone Ruggeri, Eric Hidari, David Klenerman
Published in: ChemBioChem, 2021, ISSN 1439-4227
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/cbic.202100285

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

Author(s): 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
Published in: Brain, 2021, ISSN 0006-8950
Publisher: 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

Author(s): Daniel R Whiten, Philip W Brownjohn, Steven Moore, Suman De, Alessio Strano, Yukun Zuo, Moritz Haneklaus, David Klenerman, Frederick J Livesey
Published in: Brain Communications, Issue 2/2, 2020, ISSN 2632-1297
Publisher: Oxford University Press
DOI: 10.1093/braincomms/fcaa146