Explore the words cloud of the Neurotoxic project. It provides you a very rough idea of what is the project "Neurotoxic" about.
The following table provides information about the project.
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
|Coordinator Country||United Kingdom [UK]|
|Total cost||195˙454 €|
|EC max contribution||195˙454 € (100%)|
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
|Duration (year-month-day)||from 2016-08-01 to 2018-07-31|
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|1||THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE||UK (CAMBRIDGE)||coordinator||195˙454.00|
The study of protein aggregates and how they damage neuronal cells is important in order to understand the initiation and progression of several neurodegenerative diseases - including Alzheimer’s disease (AD), Parkinson’s disease (PD). The aggregation from the native monomeric proteins to beta sheet containing amyloid structures involves the formation of different species - misfolded proteins, small soluble oligomers and finally formation of fibrils. It is believed that small oligomers are the most cytotoxic species which play a major role in neuronal loss and cell death. Although, the exact mechanism and extent of amyloid oligomer’s cytotoxicity is still unknown, one of the most consistent pathologies in neurodegenerative disease is unregulated influx of Ca2 into the cell. Individual oligomers directly disrupt cell membranes through non-specific binding at picomolar concentrations leading to the formation of ion channels, which allow Ca2 influx and can lead to cell death. Based on this observation, we will develop a single liposome assay to quantify the oligomer induced toxicity from oligomers present in human cerebrospinal fluid (CSF) from healthy controls and patients with AD and PD. Using a Ca2 sensitive fluorogenic sensor, we will monitor the oligomer induced Ca2 influx inside the liposome in real time. We will measure and compare the toxicity of synthetic oligomers of amyloid beta, alpha-synuclein, tau and PrP oligomers as a function of oligomer concentration and liposome membrane composition. We will then quantify the effect of various antibodies commonly used for treatment of AD and PD on the toxicity of synthetic oligomers and those in CSF. This novel ultra-sensitive state-of-the-art single molecule technique will provide new insights into the mechanism of oligomer induced toxicity, allowing us to identify the most toxic oligomers and the most suitable antibodies to prevent oligomer induced damage as well as having potential for early disease diagnosis.
|year||authors and title||journal||last update|
Franziska Kundel, Suman De, Patrick Flagmeier, Mathew H. Horrocks, Magnus Kjaergaard, Sarah L. Shammas, Sophie E. Jackson, Christopher M. Dobson, David Klenerman
Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity
published pages: , ISSN: 1554-8929, DOI: 10.1021/acschembio.7b01039
|ACS Chemical Biology||2019-07-25|
Patrick Flagmeier, Suman De, David C. Wirthensohn, Steven F. Lee, CÃ©cile Vincke, Serge Muyldermans, Tuomas P. J. Knowles, Sonia Gandhi, Christopher M. Dobson, David Klenerman
Ultrasensitive Measurement of Ca 2+ Influx into Lipid Vesicles Induced by Protein Aggregates
published pages: 7750-7754, ISSN: 1433-7851, DOI: 10.1002/anie.201700966
|Angewandte Chemie International Edition 56/27||2019-07-25|
Juan Alberto Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi, Christopher M. Dobson, David Klenerman, Steven Lee
Optical structural analysis of individual Î±-synuclein oligomers
published pages: , ISSN: 1433-7851, DOI: 10.1002/anie.201710779
|Angewandte Chemie International Edition||2019-07-25|
Daniel R. Whiten, Yukun Zuo, Laura Calo, Minee-Liane Choi, Suman De, Patrick Flagmeier, David C. Wirthensohn, Franziska Kundel, Rohan T. Ranasinghe, Santiago E. Sanchez, Dilan Athauda, Steven F. Lee, Christopher M. Dobson, Sonia Gandhi, Maria-Grazia Spillantini, David Klenerman, Mathew H. Horrocks
Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells
published pages: 2033-2038, ISSN: 1439-4227, DOI: 10.1002/cbic.201800209
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
Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic Î±-Synuclein Oligomers
published pages: 3492-3500, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.05.074
|Cell Reports 23/12||2019-07-25|
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
Quantifying Co-Oligomer Formation by Î±-Synuclein
published pages: , ISSN: 1936-0851, DOI: 10.1021/acsnano.8b03575
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