Affiliations: [a] Department of Neurosciences and Biomedical Technologies. University of Milano-Bicocca, Italy | [b] Ospedale San Gerardo, Monza, Italy | [c] Scientific Institute E. Medea, Bosisio Parini, Italy | Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany Tel.: +49 211 811 5358; Fax: +49 211 811 3029; E-mail: [email protected]
Correspondence:
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Corresponding author: Prof. Carlo Ferrarese, Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Ospedale S. Gerardo, Via Donizetti, 106 – 20052 Monza (MI), Italy. Tel.: +39 039 2333595; Fax: +39 039 2333586; E-mail: [email protected].
Abstract: Oxidative stress has been implicated as a common pathogenetic mechanism in neurodegenerative disorders. Central nervous system is particularly exposed to free radical injury, given its high metal content, which can catalyze the formation of oxygen free radicals, and the relatively low content of antioxidant defenses. Indeed, several studies show markers of oxidative damage – lipid peroxidation, protein oxidation, DNA oxidation and glycoxidation markers – in brain areas affected by neurodegenerative disorders. Oxidative stress damage is intimately linked to glutamate neurotoxicity – known as “excitotoxicity”. An excessive concentration of extracellular glutamate over-activates ionotropic glutamate receptors, resulting in intracellular calcium overload and a cascade of events leading to neural cell death. In this study we reviewed pathogenetic mechanisms that link oxidative stress and excitotoxicity in three neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease) and described peripheral markers of these mechanisms, that may be analyzed in patients as possible diagnostic and therapeutic tools.
