aLzINK SIGNED
Alzheimer's disease and Zinc: the missing link ?
Total Cost €
0EC-Contrib. €
0Partnership
0Views
0aLzINK project word cloud
Explore the words cloud of the aLzINK project. It provides you a very rough idea of what is the project "aLzINK" about.
Project "aLzINK" data sheet
The following table provides information about the project.
| Coordinator |
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Organization address contact info |
| Coordinator Country | France [FR] |
| Total cost | 1˙499˙947 € |
| EC max contribution | 1˙499˙947 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-03-01 to 2020-02-29 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS | FR (PARIS) | coordinator | 1˙499˙947.00 |
Map
Project objective
Alzheimer's disease (AD) is one of the most serious diseases mankind is now facing as its social and economical impacts are increasing fastly. AD is very complex and the amyloid-β (Aβ) peptide as well as metallic ions (mainly copper and zinc) have been linked to its aetiology. While the deleterious impact of Cu is widely acknowledged, intervention of Zn is certain but still needs to be figured out. The main objective of the present proposal, which is strongly anchored in the bio-inorganic chemistry field at interface with spectroscopy and biochemistry, is to design, synthesize and study new drug candidates (ligands L) capable of (i) targeting Cu(II) bound to Aβ within the synaptic cleft, where Zn is co-localized and ultimately to develop Zn-driven Cu(II) removal from Aβ and (ii) disrupting the aberrant Cu(II)-Aβ interactions involved in ROS production and Aβ aggregation, two deleterious events in AD. The drug candidates will thus have high Cu(II) over Zn selectively to preserve the crucial physiological role of Zn in the neurotransmission process. Zn is always underestimated (if not completely neglected) in current therapeutic approaches targeting Cu(II) despite the known interference of Zn with Cu(II) binding.
To reach this objective, it is absolutely necessary to first understand the metal ions trafficking issues in presence of Aβ alone at a molecular level (i.e. without the drug candidates).This includes: (i) determination of Zn binding site to Aβ, impact on Aβ aggregation and cell toxicity, (ii) determination of the mutual influence of Zn and Cu to their coordination to Aβ, impact on Aβ aggregation, ROS production and cell toxicity.
Methods used will span from organic synthesis to studies of neuronal model cells, with a major contribution of a wide panel of spectroscopic techniques including NMR, EPR, mass spectrometry, fluorescence, UV-Vis, circular-dichroism, X-ray absorption spectroscopy...
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2018 |
Bruno Aliès, Valentina Borghesani, Sabrina Noël, Stephanie Sayen, Emmanuel Guillon, Denis Testemale, Peter Faller, Christelle Hureau Mutations of Histidine 13 to Arginine and Arginine 5 to Glycine Are Responsible for Different Coordination Sites of Zinc(II) to Human and Murine Peptides published pages: 14233-14241, ISSN: 0947-6539, DOI: 10.1002/chem.201802759 |
Chemistry – A European Journal 24/53 | 2019-12-16 |
| 2019 |
Elena Atrián-Blasco, Elena Cerrada, Peter Faller, Mariano Laguna, Christelle Hureau Role of PTA in the prevention of Cu(amyloid-β) induced ROS formation and amyloid-β oligomerisation in the presence of Zn published pages: 1154-1161, ISSN: 1756-5901, DOI: 10.1039/C9MT00011A |
Metallomics 11/6 | 2019-12-16 |
| 2018 |
Amandine Conte-Daban, Maryline Beyler, Raphaël Tripier, Christelle Hureau Kinetics Are Crucial When Targeting Copper Ions to Fight Alzheimer\'s Disease: An Illustration with Azamacrocyclic Ligands published pages: 8447-8452, ISSN: 0947-6539, DOI: 10.1002/chem.201801520 |
Chemistry - A European Journal 24/33 | 2019-12-16 |
| 2019 |
Hureau, Christelle Metal Ions and Complexes in Alzheimer\'s Disease: From Fundamental to Therapeutic Perspectives published pages: , ISSN: , DOI: |
R. A. Scott. Encyclopedia of Inorganic and Bioinorganic Chemistry, John Wiley & Sons, Ltd, 2018 1 | 2019-12-16 |
| 2019 |
Paulina Gonzalez, Karolina Bossak-Ahmad, Bertrand Vileno, Nina E. Wezynfeld, Youssef El Khoury, Petra Hellwig, Christelle Hureau, Wojciech Bal, Peter Faller Triggering Cu-coordination change in Cu( ii )-Ala-His-His by external ligands published pages: 8110-8113, ISSN: 1359-7345, DOI: 10.1039/c9cc03174j |
Chemical Communications 55/56 | 2019-12-16 |
| 2016 |
Clémence Cheignon, Fabrice Collin, Peter Faller, Christelle Hureau Is ascorbate Dr Jekyll or Mr Hyde in the Cu(Aβ) mediated oxidative stress linked to Alzheimer\'s disease? published pages: 12627-12631, ISSN: 1477-9226, DOI: 10.1039/C6DT01979J |
Dalton Trans. 45/32 | 2019-05-28 |
| 2018 |
Amandine Conte-Daban, Vinita Ambike, Régis Guillot, Nicolas Delsuc, Clotilde Policar, Christelle Hureau A Metallo Pro-Drug to Target Cu II in the Context of Alzheimer\'s Disease published pages: 5095-5099, ISSN: 0947-6539, DOI: 10.1002/chem.201706049 |
Chemistry - A European Journal 24/20 | 2019-05-28 |
| 2018 |
Weixin Zhang, Yan Liu, Christelle Hureau, Anne Robert, Bernard Meunier N 4 -Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-β 1-16 published pages: 7825-7829, ISSN: 0947-6539, DOI: 10.1002/chem.201801387 |
Chemistry - A European Journal 24/31 | 2019-05-28 |
| 2017 |
Amandine Conte-Daban, Valentina Borghesani, Stéphanie Sayen, Emmanuel Guillon, Yves Journaux, Geoffrey Gontard, Laurent Lisnard, Christelle Hureau Link between Affinity and Cu(II) Binding Sites to Amyloid-β Peptides Evaluated by a New Water-Soluble UV–Visible Ratiometric Dye with a Moderate Cu(II) Affinity published pages: 2155-2162, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.6b04979 |
Analytical Chemistry 89/3 | 2019-05-28 |
| 2017 |
Elena Atrián-Blasco, Alice Santoro, Dean L. Pountney, Gabriele Meloni, Christelle Hureau, Peter Faller Chemistry of mammalian metallothioneins and their interaction with amyloidogenic peptides and proteins published pages: , ISSN: 0306-0012, DOI: 10.1039/C7CS00448F |
Chemical Society Reviews | 2019-05-28 |
| 2017 |
Amandine Conte-Daban, Bastien Boff, Andreza Candido Matias, Claudia N. Montes Aparicio, Christelle Gateau, Colette Lebrun, Giselle Cerchiaro, Isabelle Kieffer, Stéphanie Sayen, Emmanuel Guillon, Pascale Delangle, Christelle Hureau A Trishistidine Pseudopeptide with Ability to Remove Both Cu Ι and Cu ΙΙ from the Amyloid-β Peptide and to Stop the Associated ROS Formation published pages: , ISSN: 0947-6539, DOI: 10.1002/chem.201703429 |
Chemistry - A European Journal | 2019-05-28 |
| 2017 |
Elena Atrián-Blasco, Amandine Conte-Daban, Christelle Hureau Mutual interference of Cu and Zn ions in Alzheimer\'s disease: perspectives at the molecular level published pages: 12750-12759, ISSN: 1477-9226, DOI: 10.1039/C7DT01344B |
Dalton Trans. 46/38 | 2019-05-28 |
| 2018 |
Elena Atrián-Blasco, Melisa del Barrio, Peter Faller, Christelle Hureau Ascorbate Oxidation by Cu(Amyloid-β) Complexes: Determination of the Intrinsic Rate as a Function of Alterations in the Peptide Sequence Revealing Key Residues for Reactive Oxygen Species Production published pages: 5909-5915, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.8b00740 |
Analytical Chemistry 90/9 | 2019-05-28 |
| 2016 |
Bruno Alies, Amandine Conte-Daban, Stéphanie Sayen, Fabrice Collin, Isabelle Kieffer, Emmanuel Guillon, Peter Faller, Christelle Hureau Zinc(II) Binding Site to the Amyloid-β Peptide: Insights from Spectroscopic Studies with a Wide Series of Modified Peptides published pages: 10499-10509, ISSN: 0020-1669, DOI: 10.1021/acs.inorgchem.6b01733 |
Inorganic Chemistry 55/20 | 2019-05-28 |
| 2017 |
Clémence Cheignon, Megan Jones, Elena Atrián-Blasco, Isabelle Kieffer, Peter Faller, Fabrice Collin, Christelle Hureau Identification of key structural features of the elusive Cu–Aβ complex that generates ROS in Alzheimer’s disease published pages: 5107-5118, ISSN: 2041-6520, DOI: 10.1039/C7SC00809K |
Chem. Sci. 8/7 | 2019-05-28 |
| 2017 |
Valentina Borghesani, Bruno Alies, Christelle Hureau Cu II Binding to Various Forms of Amyloid-β Peptides: Are They Friends or Foes? published pages: , ISSN: 1434-1948, DOI: 10.1002/ejic.201700776 |
European Journal of Inorganic Chemistry | 2019-05-28 |
| 2016 |
Clémence Cheignon, Peter Faller, Denis Testemale, Christelle Hureau, Fabrice Collin Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production published pages: 1081-1089, ISSN: 1756-5901, DOI: 10.1039/C6MT00150E |
Metallomics 8/10 | 2019-05-28 |
| 2018 |
Elena Atrián-Blasco, Paulina Gonzalez, Alice Santoro, Bruno Alies, Peter Faller, Christelle Hureau Cu and Zn coordination to amyloid peptides: From fascinating chemistry to debated pathological relevance published pages: 38-55, ISSN: 0010-8545, DOI: 10.1016/J.CCR.2018.04.007 |
Coordination Chemistry Reviews 371 | 2019-05-28 |
| 2016 |
Amandine Conte-Daban, Adam Day, Peter Faller, Christelle Hureau How Zn can impede Cu detoxification by chelating agents in Alzheimer\'s disease: a proof-of-concept study published pages: 15671-15678, ISSN: 1477-9226, DOI: 10.1039/C6DT02308H |
Dalton Trans. 45/39 | 2019-05-28 |
| 2017 |
Arlette Itken-Fuder, Christelle Hureau Copper Binding to Amyloid-β Peptides published pages: , ISSN: 2190-3735, DOI: 10.1002/chemv.201700081 |
ChemViews | 2019-05-28 |
| 2018 |
Paulina Gonzalez, Karolina Bossak, Ewelina Stefaniak, Christelle Hureau, Laurent Raibaut, Wojciech Bal, Peter Faller N-Terminal Cu-Binding Motifs (Xxx-Zzz-His, Xxx-His) and Their Derivatives: Chemistry, Biology and Medicinal Applications published pages: 8029-8041, ISSN: 0947-6539, DOI: 10.1002/chem.201705398 |
Chemistry - A European Journal 24/32 | 2019-05-28 |
| 2018 |
C. Cheignon, M. Tomas, D. Bonnefont-Rousselot, P. Faller, C. Hureau, F. Collin Oxidative stress and the amyloid beta peptide in Alzheimer’s disease published pages: 450-464, ISSN: 2213-2317, DOI: 10.1016/j.redox.2017.10.014 |
Redox Biology 14 | 2019-05-28 |
Are you the coordinator (or a participant) of this project? Plaese send me more information about the "ALZINK" project.
For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.
Send me an email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.
Thanks. And then put a link of this page into your project's website.
The information about "ALZINK" are provided by the European Opendata Portal: CORDIS opendata.