Interplay of Cu,Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes.
Reactive oxygen and nitrogen species (ROS and RNS) have been extensively recognized as important signaling molecules implicated in physiological processes such as gene expression, cell differentiation and immune activation. Nevertheless, continuous production of these species may produce oxidative and/or nitrosative stress resulting in cell damage and ultimately leading to cell death. Due to the high oxygen consumption and relative poor antioxidant defense, the central nervous system is highly susceptible to ROS- and RNS-mediated toxicity. Actually, the oxidative and nitrosative stress have been implicated in the pathogenesis of neurodegeneration of a large variety of neurological disorders. This review will cover some aspects of the involvement of ROS- and RNS-mediated apoptotic processes occurring in cellular models of familial amyotrophic lateral sclerosis (FALS), in particular the cases associated with mutations in SOD1, the gene encoding Cu,Zn superoxide dismutase (Cu,Zn SOD). A possible role for proteasome in the inhibition of neurodegenerative process by balancing ROS and RNS species is envisaged on the basis of evidence provided by results obtained from studies on this experimental model.
Rotilio
Giuseppe
G
Department of Biology, University of Rome Tor Vergata, Rome, Italy. rotilio@bio.uniroma2.it
Aquilano
Karia
K
Ciriolo
Maria Rosa
MR
D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D009097:Multienzyme Complexes; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D010100:Oxygen