0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
LIST OF PARTICIPATING UNITS
U.O. 1 – IRCCS Istituto Neurologico Mediterraneo Neuromed –
Fabrizio Eusebi
U.O. 2 – Università di Roma La Sapienza, Dipartimento Fisiologia
Umana e Farmacologia – Cristina Limatola
U.O. 3 – CNR, Istituto di Biologia e Patologia Molecolare –
Claudio Passananti
U.O. 4 – Fondazione Santa Lucia IRCCS, Laboratorio di Neurofisiologia –
Diego Centonze
U.O. 5 – Università di Roma La Sapienza, Dipartimento di Medicina
Extrapiramidale – Francesco Violi
U.O. 6 – San Raffele Pisana IRCCS – Daniela Melchiorri
U.O. 7 – IRCCS Auxologico Milano – Vincenzo Silani
DESCRIPTION OF THE PROJECT
What is already known on the subject
Inflammation is implicated in the progressive nature of neurodegenerative
diseases, but the inflammatory mechanisms are poorly understood; and a
growing body of evidence has shown that similar inflammatory mechanisms
may participate in the pathological changes observed in Huntington’s disease
(HD), and amyotrophic lateral sclerosis (ALS), including cognitive impairment.
Specifically, there is increasing awareness that blood-borne cells or signals
may participate to neurological disorders such as neurodegenerative diseases,
by virtue of a leaky blood brain barrier which on the other hand may
help in therapeutic approaches following systemic drug administration. Evidence
is accumulating to indicate that chronic neurodegenerative disorders
such as HD and ALS are caused by a combination of events, namely accumulation
of aberrant or misfolded proteins, excitotoxic insult, oxidative stress,
mitochondrial injury, synaptic failure, altered metal homeostasis and failure
of axonal and dendritic transport, that impair normal neuronal function leading
to neuronal death. Each of these events is related to specific molecular
pathways which, if they are disclosed in their common mechanisms, may lead
to therapeutic treatments in clinical practice. Aim of this project of research is
to further investigate inflammatory mechanisms and their molecular pathways
associated to neurodegenerative diseases, HD and ALS, to provide a
foundation for their treatments. In addition, we are interested in disclosing
the neuroprotective role of Che-1/AATF, a multivalent factor that is involved in
apoptotic signalling, modulating the balance between death and survival, and
of the chemokine fractalkine, whose neuroprotective activity has been
recently demonstrated in several neurodegenerative diseases. Such an investigation
will be carried out with a variety of experimental approaches using cell
and molecular biology, pharmacological and electrophysiological techniques.
746 2009