NEURO.GSK3

GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment

Coordinatore	KATHOLIEKE UNIVERSITEIT LEUVEN    more  Organization address address: Oude Markt 13 city: LEUVEN postcode: 3000 contact info Titolo: Ms. Nome: Tine Cognome: Heylen Email: send email Telefono: +32 16 326520 Fax: +32 16 326515
Nazionalità Coordinatore	Belgium [BE]
Sito del progetto	http://med.kuleuven.be/neurogsk3/gsk3.html
Totale costo	5˙082˙027 €
EC contributo	3˙573˙842 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2007-B
Funding Scheme	CP-FP
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-10-01   -   2011-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	KATHOLIEKE UNIVERSITEIT LEUVEN  Organization address address: Oude Markt 13 city: LEUVEN postcode: 3000 contact info Titolo: Ms. Nome: Tine Cognome: Heylen Email: send email Telefono: +32 16 326520 Fax: +32 16 326515	BE (LEUVEN)	coordinator	0.00
2	INTERNATIONAL INSTITUTE OF MOLECULAR AND CELL BIOLOGY  Organization address address: ks. Trojdena 4 city: Warsaw postcode: 02-109 contact info Titolo: Dr. Nome: Urszula Cognome: Wyrzykowska Email: send email Telefono: +48 22 5970713 Fax: +48 22 5970715	PL (Warsaw)	participant	0.00
3	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN  Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 contact info Titolo: Prof. Nome: Jochen Cognome: Herms Email: send email Telefono: +49 89 21 80 78 010 Fax: +49 89 21 80 78 037	DE (MUENCHEN)	participant	0.00
4	MEDICAL RESEARCH COUNCIL  Organization address address: NORTH STAR AVENUE POLARIS HOUSE city: SWINDON postcode: SN2 1FL contact info Titolo: Ms. Nome: Elizabeth Cognome: Cutler Email: send email Telefono: + 44 (0) 1223402357 Fax: + 44 (0)1223 412 515	UK (SWINDON)	participant	0.00
5	NOSCIRA SA  Organization address address: Calle Jose Abascal 2 city: MADRID postcode: 28003 contact info Titolo: Ms. Nome: Rebeca Cognome: García Email: send email Telefono: +34 91 806 11 30 Fax: +34 91 803 46 60	ES (MADRID)	participant	0.00
6	TECHNISCHE UNIVERSITAET DARMSTADT  Organization address address: Karolinenplatz 5 city: DARMSTADT postcode: 64289 contact info Titolo: Prof. Nome: Boris Cognome: Schmidt Email: send email Telefono: +49 6151 16 30 75 Fax: +49 6151 163278	DE (DARMSTADT)	participant	0.00
7	TEL AVIV UNIVERSITY  Organization address address: RAMAT AVIV city: TEL AVIV postcode: 69978 contact info Titolo: Ms. Nome: Lea Cognome: Pais Email: send email Telefono: +972 3 640 8774 Fax: +972 3 640 5483	IL (TEL AVIV)	participant	0.00

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 Obiettivo del progetto (Objective)

'Neuronal circuits in mammalian brain act predominantly via excitatory synapses on dendritic spines. Formation of new spines in adult brain constitutes the structural basis of neuronal plasticity. The underlying molecular mechanisms remain largely unknown but depend essentially on kinase-dependent signalling pathways. Final formation of synapses on spines depends on dynamic interactions of microtubuli and actin-filaments that are also controlled by kinases. Deterioration of these processes to different extents are thought to cause the cognitive decline in normal ageing as well in Alzheimer's disease (AD) and familial fronto-temporal dementia (FTD). Protein tau is a microtubule associated protein and GSK-3 kinases are proposed as the major tau-kinases in vivo. Their exact contributions remain to be functionally defined in vivo both in normal neuronal plasticity and in degeneration. We develop pre-clinical models for AD and FTD that have tauopathy in common as essential pathogenic component and will explore the GSK-3 kinases in vivo by manipulating their activity genetically, pharmacologically and biochemically. Inhibitors are wanted that are effective and specific and enter brain in vivo. This proposal engages in three activities: (i) elucidate physiological functions of GSK-3 kinases in synaptic plasticity in adult and ageing brain, and in degenerating brain; define fundamental neuron-specific functions of GSK-3 kinases in vivo in novel mouse models; define contributions of GSK-3 kinases to amyloid and to tau pathology, separately and combined in vivo in validated mouse models (ii) design novel inhibitors of GSK-3 kinases and alternative tools to inhibit GSK-3 activity in vivo (iii) test pharmacological and peptidometic inhibitors of GSK-3 in validated mouse models of neurodegeneration for their restorative potential; analyse their mode of action and their acute and chronic effects by multi-parametric analysis'