0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
according to techniques already set up in this lab: polarization of mitochondria,
intracellular ATP, activity of mitochondrial dehydrogenases, mitochondrial
GSH/GSSG ratio [Beretta et al. 2003; Carrì et al. 1997; Cozzolino et al. 2004;
Cozzolino et al. 2006; Ferri et al. 2006]. Activity of mitochondrial complexes
will be studied by spectrofotometric techniques, using the appropriate substrate/inhibitors
[Ferri et al. 2006]. Alteration of mitochondria morphology, that
has been reported to characterize these same cells overexpressing mutSOD1
[Ferri et al. 2008], will be valuated by standard immunofluorescence methods.
EXPECTED CONSEQUENCES FOR HUMAN PATHOLOGY AND THERAPY
The completion of the different goals of this study will pursue two main
objectives:
1) It will lead to a better understanding of the role and the mechanisms
of mitochondrial dysfunction and oxidative stress in ALS.
2) Despite a huge body of evidence showing that oxidative stress may be
involved in the pathology, results from clinical trials for ALS that are based on
anti-oxidant strategies have so far yielded unimpressive results. Many of the
antioxidant therapies tested thus far may not have been effective because they
are not based on inhibition of a validated therapeutic target. For these reason,
identification of new specific pathways involved in the pathology will offer
new opportunities to devise effective tools for the treatment of the disease.
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568 2009