0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
presence of agonists and/or allosteric modulators of different kind of mGlu
receptors.
P.U.2: In order to understand the mechanisms underlying chemo -
kine·induced neuroprotection, this Unit aims to investigate the role of gliareleased
factors, such as adenosine, in the neuroprotective activities of the
chemokine fractalkine. In this context, the Unit will investigate whether
Adenosine Receptor I may coexist and cross-talk wilh presynaptic receptors,
whose activation is known to elicit the release of glutamate.
P.U.3: In order to study the neuroprotective role of the anti-apoptotic factor
Che-1 in neurodegenerative diseases, this Unit intends to study Che-1
expression and functions in physiological and neuro-pathological conditions,
taking advantage of the available HD and ASL cell lines and mice model
systems.
P.U.4: In order to clarify the role of the endocannabinoid system in the
pathophysiology of experimental HD, ALS and MS, this Unit will measure
synaptic transmission in three models of inflammatory neurodegeneration, by
means of neurophysiological recordings in corticostriatal brain slices upon
administration of agonists and/or modulator of endocannabinoid receptors.
P.U.5: In order to assess the contribution of oxidative stress reagents to
inflammation and subsequent neurodegeneration, this Unit aims to develop a
method to measure platelet gp91phox in vivo and analyse its activation in
neurodegenerative diseases, as ALS. This will allow to determine the rate of
gp91phox activation in ALS patients, who could have all up-regulation of the
NADPH oxidase.
P.U.6: In order to unveil possible common therapeutic strategies against
different pathologies sharing over-expression of a-synuclein, this Unit will use
cellular and animal models of a-synuclein-induced neurodegeneration to
study the protective role of: (a) neurotrophic factors; (b) ligands of both
ionotropic and metabotropic glulamate receptors. A protective role of glutamate
receptor ligands is predicted on the basis of their role in neurodegeneration
associated with Parkinson’s disease.
P.U.7: In order to understand the mechanisms underlying the neuronal
and glial cell dysfunction observed in the early stage of HD, this Unit will
investigate the effects of huntingtin on the production of TGFb1. The aim is to
identify alteration of TGFb1 pathway in biological sample of HD patients.
Aim of the project is also to: a) set up a bank of biologicat samples; b) to
obtain fibroblast and myoblast primary cell lines from skin and muscle biopsies;
c) to made available to all Units the animal ALS-model G93A mice and
the HD-models R6/2, expressing the mutated HD exon 1 gene, or YAC128
mice, expressing the mutated HD full length gene; d) to improve the clinical
genetic data bank for HD already setup at the Neuromed.
GENERAL TRANSFERIBILITY AND POTENTIAL IMPACT OF RESULTS
This is a translational project, in which cellular and preclinical data are
aimed at the identification of novel therapeutic targets for neurodegenerative
disorders. These targets will be identified on the ground of mechanisms of
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