Antioxidants in Down syndrome

Abstract

Individuals with Down syndrome (DS) have high levels of oxidative stress throughout the lifespan. Mouse models of DS share some structural and functional abnormalities that parallel findings seen in the human phenotype. Several of the mouse models show evidence of cellular oxidative stress and have provided a platform for antioxidant intervention. Genes that are overexpressed on chromosome 21 are associated with oxidative stress and neuronal apoptosis. The lack of balance in the metabolism of free radicals generated during processes related to oxidative stress may have a direct role in producing the neuropathology of DS including the tendency to Alzheimer disease (AD). Mitochondria are often a target for oxidative stress and are considered to be a trigger for the onset of the AD process in DS. Biomarkers for oxidative stress have been described in DS and in AD in the general population. However, intervention trials using standard antioxidant supplements or diets have failed to produce uniform therapeutic effect. This chapter will examine the biological role of oxidative stress in DS and its relationship to abnormalities in both development and aging within the disorder. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

Age‐Related Cortical Thickness Reduction in Non‐Demented Down's Syndrome Subjects

“…Other authors suggested that controlled supplementation with antioxidant, physical activity and regular exercise could be used to improve the cognitive functions . Prophylactic trial may hold more encouragement in DS and early intervention with strategically developed antioxidants may positively impact intellectual functioning decades before dementia sets in …”

HNE-modified proteins in Down syndrome: Involvement in development of Alzheimer disease neuropathology

“…OS represents an imbalance between the production of ROS and the efficiency of antioxidant systems - antioxidant compounds and antioxidant enzymes - to detoxify the reactive intermediates or to repair the oxidative damage [18, 19]. High levels of OS-induced by-products have been detected in brain tissue from DS [19, 20].…”

Persistence of the benefit of an antioxidant therapy in children and teenagers with Down syndrome

“…There is consequently a gene dosage effect in DS leading to $50% greater levels of SOD-1 and elevated endogenous production of hydrogen peroxide (H 2 O 2 ), and potentially of hydroxyl radical ( OH) (Garlet et al, 2013;Lott, 2012), which is the most reactive and deleterious ROS inducing damage in proteins, lipids and DNA (Halliwell & Gutteridge, 2007).…”