Opendata, web and dolomites

aLzINK SIGNED

Alzheimer's disease and Zinc: the missing link ?

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 aLzINK 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.

biochemistry    underestimated    always    alone    toxicity    inorganic    aberrant    first    spectroscopy    linked    diseases    events    synaptic    physiological    spectroscopic    peptide    certain    candidates    dichroism    model    metallic    understand    cleft    spectrometry    organic    site    social    trafficking    bio    ad    therapeutic    neurotransmission    zn    absorption    anchored    amyloid    span    uv    serious    contribution    copper    preserve    intervention    ultimately    synthesis    disease    vis    beta    binding    circular    techniques    fastly    mankind    fluorescence    interactions    panel    epr    synthesize    figured    chemistry    acknowledged    mutual    bound    zinc    despite    selectively    mass    cu    ros    economical    metal    aetiology    ions    disrupting    alzheimer    nmr    cells    impacts    completely    drug    co    removal    interface    interference    deleterious    aggregation    ray    localized    cell    influence    mainly    molecular    absolutely    neuronal    ligands   

Project "aLzINK" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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.

More projects from the same programme (H2020-EU.1.1.)

NanoPD_P (2020)

High throughput multiplexed trace-analyte screening for diagnostics applications

Read More  

NEUROPRECISE (2019)

Precision medicine in traumatic brain injury using individual neurosteroid response

Read More  

SUExp (2018)

Strategic Uncertainty: An Experimental Investigation

Read More