Oxidative Stress and Mitochondrial Dysfunction in Down Syndrome

  • Giovanni PaganoEmail author
  • Giuseppe Castello
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 724)


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.


Alzheimer Disease Down Syndrome Mitochondrial Dysfunction Fanconi Anaemia Lipoic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  1. 1.CROMCancer Research CenterMercoglianoItaly

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