Characterising protein oligomers and their role in neurodegenerative disease in humans

Informazioni relative al progetto

Oligomers

ID dell’accordo di sovvenzione: 669237

DOI 10.3030/669237

Progetto chiuso

Data della firma CE 25 Agosto 2015

Data di avvio 1 Settembre 2015

Data di completamento 31 Agosto 2021

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale € 2 499 551,00

Contributo UE € 2 499 551,00

Coordinato da

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

Pubblicazioni

Peer reviewed articles (25)

Filamentous Aggregates Are Fragmented by the Proteasome Holoenzyme

Autori: Rachel Cliffe, Jason C. Sang, Franziska Kundel, Daniel Finley, David Klenerman, Yu Ye
Pubblicato in: Cell Reports, Numero 26/8, 2019, Pagina/e 2140-2149.e3, ISSN 2211-1247
Editore: 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

Autori: Suman De, David Klenerman
Pubblicato in: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Numero 1867/10, 2019, Pagina/e 870-878, ISSN 1570-9639
Editore: Elsevier BV
DOI: 10.1016/j.bbapap.2018.12.010

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

Autori: Jason C. Sang, Eric Hidari, Georg Meisl, Rohan T. Ranasinghe, Maria Grazia Spillantini, David Klenerman
Pubblicato in: Communications Biology, Numero 4/1, 2021, ISSN 2399-3642
Editore: Communication Biology
DOI: 10.1038/s42003-021-02126-w

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

Autori: 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
Pubblicato in: Science Advances, 2021, ISSN 2375-2548
Editore: AAAS
DOI: 10.1126/sciadv.abh1448

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

Autori: 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
Pubblicato in: Brain Communications, Numero 3/3, 2021, ISSN 2632-1297
Editore: 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

Autori: 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
Pubblicato in: Brain Communications, Numero 2/1, 2020, ISSN 2632-1297
Editore: Oxford University Press
DOI: 10.1093/braincomms/fcaa010

Optical structural analysis of individual α-synuclein oligomers

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

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

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

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

Autori: 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
Pubblicato in: BMC Biology, Numero 15/1, 2017, ISSN 1741-7007
Editore: BioMed Central
DOI: 10.1186/s12915-017-0390-6

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

Autori: 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
Pubblicato in: Angewandte Chemie International Edition, Numero 56/27, 2017, Pagina/e 7750-7754, ISSN 1433-7851
Editore: John Wiley & Sons Ltd.
DOI: 10.1002/anie.201700966

Inhibiting the Ca 2+ Influx Induced by Human CSF

Autori: 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
Pubblicato in: Cell Reports, Numero 21/11, 2017, Pagina/e 3310-3316, ISSN 2211-1247
Editore: Cell Press
DOI: 10.1016/j.celrep.2017.11.057

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

Autori: 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
Pubblicato in: Cell Reports, Numero 23/12, 2018, Pagina/e 3492-3500, ISSN 2211-1247
Editore: Cell Press
DOI: 10.1016/j.celrep.2018.05.074

Nanoscopic characterization of individual endogenous protein aggregates in human neuronal cells

Autori: 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
Pubblicato in: ChemBioChem, 2018, ISSN 1439-4227
Editore: John Wiley & Sons Ltd.
DOI: 10.1002/cbic.201800209

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

Autori: 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.
Pubblicato in: ACS Chemical Neuroscience (2018), 2018, Pagina/e 1276–1282, ISSN 1948-7193
Editore: American Chemical Society
DOI: 10.17863/CAM.25419

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

Autori: Christopher G. Taylor, Georg Meisl, Mathew H. Horrocks, Henrik Zetterberg, Tuomas P. J. Knowles, David Klenerman
Pubblicato in: Analytical Chemistry, Numero 90/17, 2018, Pagina/e 10385-10393, ISSN 0003-2700
Editore: 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

Autori: Anna Drews, Jennie Flint, Nadia Shivji, Peter Jönsson, David Wirthensohn, Erwin De Genst, Cécile Vincke, Serge Muyldermans, Chris Dobson, David Klenerman
Pubblicato in: Scientific Reports, Numero 6/1, 2016, ISSN 2045-2322
Editore: Nature Publishing Group
DOI: 10.1038/srep31910

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

Autori: 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
Pubblicato in: Nature Communications, Numero 10/1, 2019, ISSN 2041-1723
Editore: 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

Autori: 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
Pubblicato in: Acta Neuropathologica Communications, Numero 7/1, 2019, ISSN 2051-5960
Editore: BioMed Central
DOI: 10.1186/s40478-019-0777-4

Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale

Autori: 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
Pubblicato in: Nano Letters, Numero 18/12, 2018, Pagina/e 7494-7501, ISSN 1530-6984
Editore: 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

Autori: 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
Pubblicato in: Acta Neuropathologica, Numero 137/1, 2019, Pagina/e 103-120, ISSN 0001-6322
Editore: 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

Autori: 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
Pubblicato in: Communications Biology, Numero 3/1, 2020, ISSN 2399-3642
Editore: Nature research
DOI: 10.1038/s42003-020-0792-9

Quantifying Co-Oligomer Formation by α-Synuclein

Autori: 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
Pubblicato in: ACS Nano, Numero 12/11, 2018, Pagina/e 10855-10866, ISSN 1936-0851
Editore: American Chemical Society
DOI: 10.1021/acsnano.8b03575

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

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

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

Autori: 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
Pubblicato in: Brain, 2021, ISSN 0006-8950
Editore: 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

Autori: Daniel R Whiten, Philip W Brownjohn, Steven Moore, Suman De, Alessio Strano, Yukun Zuo, Moritz Haneklaus, David Klenerman, Frederick J Livesey
Pubblicato in: Brain Communications, Numero 2/2, 2020, ISSN 2632-1297
Editore: Oxford University Press
DOI: 10.1093/braincomms/fcaa146