restorative plasticity at corticostriatal excitatory synapses a project funded by the european union...

RESTORATIVE PLASTICITY AT CORTICOSTRIATAL EXCITATORY SYNAPSESA project funded by the European Union Seventh Framework ProgrammeFP7/2007-2013 under grant agreement n° 222918

Graph and Illustrations:The Visual Agency

PARKINSON’S DISEASE (PD)is one of the most common

chronic progressive neurodegenerative diseaseshas a prevalence of 1.2 million people in Europe

and an annual cost of 11 billion Euros,

being one of the 12 most costly brain diseases in Europe

Di Luca M, Baker M, Corradetti R, Kettenmann H, Mendlewicz J, Olesen J, Ragan I, Westphal M. Eur J Neurosci. 2011

COST OF DISORDERS OF THE BRAIN IN EUROPE

Estimates in 2004

Estimates in 2010

European Neuropsychopharmacology (2011) 21, 718-779

(1) Referred to as “effective disorders” in 2005, (2) includes only incident cases in 2010, (3) weighted mean from all countries and diagnoses(5) including also persons with zero costs, (6) excluding indirect costs, (7) excluding PTSD.

COST OF DISORDERS OF THE BRAIN IN EUROPE

Estimates in 2004

Estimates in 2010

European Neuropsychopharmacology (2011) 21, 718-779

(1) Referred to as “effective disorders” in 2005, (2) includes only incident cases in 2010, (3) weighted mean from all countries and diagnoses(5) including also persons with zero costs, (6) excluding indirect costs, (7) excluding PTSD.

The cost of brain diseases in Europe has been estimated 798 billion euros

(The economic cost of brain disorders in Europe. Olesen et al, Eur J Neurol. 2012)

WHAT DO WE ASK TO RESEARCH?

How to impact on disease onset and progression,to effectively help those citizens

LEAVING WITH PD

A strong translational character:Understanding the brain functioning at molecular, cellularand system level is essential to unravel pathogenesis of

brain disease

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A spine is moving!A confocal microscopy analysis

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IN VITRO...

PureStriatum

Striatumco-culturedwith cortex

IN VIVO...AAV α-synuclein model of PD: progressive neurodegeneration

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3 NOVELHYPOTHESES TO CURE

METABOTROPIC GLUTAMATE RECEPTOR TYPE 5 (mGluR5) AS A TARGET FOR THE TREATMENT OF L-DOPA-INDUCED DYSKINESIA

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SYNAPTIC LOCALIZATOR OF NR2A SUBUNITIN CHRONIC L-DOPA TREATED ANIMALS MODULATES DYSKINETIC MOTOR BEHAVIOUR

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TAT-2ATAT-2A(-SDV)

Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg - Lys-Met-Pro-Ser-Ile-Glu-Ser-Asp-ValTyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg - Lys-Met-Pro-Ser-Ile-Glu

TAT NR2A C-tail

REBALANCE OF STRIATAL NMDA/AMPA RECEPTOR RATIO UNDERLIES THE REDUCED EMERGENCE OF DYSKINESIA DURING D2-LIKE DOPAMINE AGONIST TREATMENT

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.THANK YOU

Graph and Illustrations:The Visual Agency