title: Oxidative stress and mitochondrial dysfunction in Down syndrome.
abstract: Down syndrome (DS) or trisomy 21 is the genetic disease with highest prevalence displaying phenotypic features that both include neurologic deficiencies and a number of clinical outcomes. DS-associated neurodegeneration recalls the clinical course of Alzheimer disease (AD), due to DS progression toward dementia and amyloid plaques reminiscent of AD clinical course. Moreover, DS represents one of the best documented cases of a human disorder aetiologically related to the redox imbalance that has long been attributed to overexpression of Cu,Zn-superoxide dismutase (SOD-1), encoded by trisomic chromosome 21. The involvement of oxidative stress has been reported both in genes located else than at chromosome 21 and in transcriptional regulation of genes located at other chromosomes. Another well documented hallmark of DS phenotype is represented by a set of immunologic defects encompassing a number of B and T-cell functions and cytokine production, together prompting a proinflammatory state. In turn, this condition can be directly interrelated with an in vivo prooxidant state. As an essential link to oxidative stress, mitochondrial dysfunctions are observed whenever redox imbalances occur, due to the main roles of mitochondria in oxygen metabolism and this is the case for DS. Ultrastructural and biochemical abnormalities were reported in mitochondria from human DS patients and from trisomy 16 (Ts16) mice, to be reviewed in this chapter. Together, in vivo alterations of mitochondrial function are consistent with a prooxidant state as a phenotypic hallmark in DS.
authors.affiliation: Cancer Research Center, Mercogliano, Italy. gbpagano@tin.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pagano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
mesh_terms: D000818:Animals; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000150:complications*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000150:complications*; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1