title: Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals.
abstract: Amyotrophic lateral sclerosis is one of the most common neurodegenerative disorders, with an incidence of about 1/100,000. One of the typical features of this progressive, lethal disease, occurring both sporadically and as a familial disorder, is degeneration of cortical and spinal motor neurones. Present evidence indicates that loss of neurones in patients results from a complex interplay among oxidative injury, excitotoxic stimulation, dysfunction of critical proteins and genetic factors. This review focuses on existing evidence that oxidative stress is a major culprit in the pathogenesis of amyotrophic lateral sclerosis. An increase in reactive oxygen species and in products of oxidation has been observed both in post-mortem samples and in experimental models for ALS. This increase may be consequent to altered metabolism of copper and iron ions, that share the property to undergo redox cycling and generate reactive oxygen species. Metal-mediated oxidative stress would lead to several intracellular alterations and contribute to the induction of cell death pathways.
authors.affiliation: Dipartimento di Biologia, Università di Roma "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy. carri@Bio.uniroma2.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Carrí
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferri
authors.forename: Mauro
authors.initials: M
authors.lastname: Cozzolino
authors.forename: Lilia
authors.initials: L
authors.lastname: Calabrese
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rotilio
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D006706:Homeostasis; D006801:Humans; D008670:Metals / Q000378:metabolism*; D009046:Motor Neurons; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress
chemical_list: D008670:Metals