title: Misfolded proteins and neurodegeneration: role of non-native cytochrome c in cell death.
abstract: Intermediates play a relevant role in the protein-folding process, because the onset of diseases of genetic nature is usually coupled with protein misfolding and the formation of stable intermediate species. This article describes and briefly discusses the mechanisms considered responsible, at molecular level, for a number of neurodegenerative diseases. In particular, interest is focused on the newly discovered role of cytochrome c in programmed cell death (apoptosis), consisting of acquisition of powerful cardiolipin-specific peroxidase action. Cardiolipin oxidation induces cytochrome c detachment from the mitochondrial membrane and favors the accumulation of products releasing proapoptotic factors. Cytochrome c showing peroxidase activity has non-native structure, and shows enhanced access of the heme catalytic site to small molecules, such as H(2)O(2). The strict correlation linking cytochrome c with the onset of neurodegenerative disorders is described and the therapeutic approach discussed.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, Rome, Italy. santucci@med.uniroma2.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Santucci
authors.forename: Federica
authors.initials: F
authors.lastname: Sinibaldi
authors.forename: Antonella
authors.initials: A
authors.lastname: Patriarca
authors.forename: Daniele
authors.initials: D
authors.lastname: Santucci
authors.forename: Laura
authors.initials: L
authors.lastname: Fiorucci
mesh_terms: D017209:Apoptosis; D002308:Cardiolipins / Q000378:metabolism; D045304:Cytochromes c / Q000502:physiology*; D006801:Humans; D009410:Nerve Degeneration / Q000209:etiology*; D009195:Peroxidase / Q000378:metabolism; D057165:Proteostasis Deficiencies
chemical_list: D002308:Cardiolipins; D045304:Cytochromes c; D009195:Peroxidase