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ConCorND SIGNED

Connectivity Correlate of Molecular Pathology in Neurodegeneration

Total Cost €

0

EC-Contrib. €

0

Partnership

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 ConCorND project word cloud

Explore the words cloud of the ConCorND project. It provides you a very rough idea of what is the project "ConCorND" about.

alteration    socioeconomic    degeneration    nds    elucidate    selective    gap    ataxia    govern    spinocerebellar    paralleling    triggers    excitatory    neuron    mid    hypothesis    revealed    mechanisms    pc    health    correlate    network    vulnerable    functioning    mouse    debilitating    pathogenic    map    conceptual    initiates    cell    inputs    cascades    silencing    life    compensatory    circuit    pcs    exists    fibers    diseases    systematic    deficits    dependency    signature    model    excitability    climbing    neurons    selectively    cf    alterations    onto    altering    connectomics    disease    neurodegeneration    sca    modifications    altered    synaptic    dysfunction    structural    circuitry    intrinsic    proteomics    pathomechanisms    first    cfs    enormous    maladaptive    exist    postsynaptic    connectome    presynaptic    conditional    signaling    enigmatic    models    nd    degenerative    cerebellar    progressive    burden    purkinje    earliest    amplifying    spectrum    sca1    arise    pharmacogenetics    trigger    therapies    suboptimal    regulate    neurodegenerative    delineate    molecular    transcriptomics    incurable    pathology    dysfunctional    entire   

Project "ConCorND" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAET BERN 

Organization address
address: HOCHSCHULSTRASSE 6
city: BERN
postcode: 3012
website: http://www.unibe.ch

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 Switzerland [CH]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAET BERN CH (BERN) coordinator 2˙000˙000.00

Map

 Project objective

Neurodegenerative diseases (NDs) are incurable, debilitating conditions, arise mid-late in life, represent an enormous health and socioeconomic burden and no therapies exist. An enigmatic finding in NDs is the early and selective alteration in intrinsic excitability of vulnerable neurons paralleling changes in its circuitry. However, a gap in understanding exists in ND field about the cause of these alterations and whether these modifications regulate degenerative pathomechanisms. Our recent study, examining mechanisms of Purkinje cell (PC) degeneration in Spinocerebellar ataxia type 1 (SCA1) revealed that the earliest cerebellar alterations occur in the major excitatory inputs onto PCs, the climbing fibers (CFs). Based on this, we propose a novel three-step model of neurodegeneration: First, suboptimal functioning of the presynaptic inputs initiates signaling deficits in target PCs. Second, those alterations trigger maladaptive responses such as altered intrinsic PC excitability, thus amplifying pathogenic cascades. Third, at network level progressive dysfunction triggers compensatory synaptic modifications within the cerebellar circuitry. In this proposal, we will test our new hypothesis for NDs on SCA1 and this will be the first study to test circuit-dependency in NDs by selectively silencing presynaptic inputs and examining molecular responses in the postsynaptic neuron. Specifically, we will 1) Identify the dysfunctional CF associated molecular signature in PCs. 2) Elucidate mechanisms involved in altering intrinsic PC excitability. 3) Map the connectome for a structural correlate of the pathology. Using conditional mouse models, pharmacogenetics, transcriptomics, proteomics and connectomics, we will delineate molecular alterations that govern disease from compensatory alterations. Our systematic approach will not only impact SCA related therapies but the entire spectrum of NDs and has the potential to change the conceptual approach of future studies on NDs.

 Publications

year authors and title journal last update
List of publications.
2018 Federica Pilotto, Smita Saxena
Epidemiology of inherited cerebellar ataxias and challenges in clinical research
published pages: 2514183X1878525, ISSN: 2514-183X, DOI: 10.1177/2514183x18785258
Clinical and Translational Neuroscience 2/2 2019-04-25

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The information about "CONCORND" are provided by the European Opendata Portal: CORDIS opendata.

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