Oxidative stress and neural dysfunction in Down Syndrome

Total or partial trisomy of chromosome 21 occurs with relatively high frequ ency and is responsible for the occurrence of Down syndrome. Phenotypically , individuals with Down syndrome display characteristic morphological featu res and a variety of clinical disorders. One of the challenges for research ers in this field has been to ascertain and understand the relationship bet ween the Down syndrome phenotype with the gene dosage effect resulting from trisomy of chromosome 21. Much attention therefore, has been given towards investigating the consequences of overexpressing chromosome 21-linked gene s. In particular, an extensive analysis of SOD1 and APP have provided impor tant insights as to how perturbations in the expression of their respective genes may contribute to the Down syndrome phenotype. In this review we wil l highlight studies which support a key role for SOD1 and APP in the pathog enesis of neural abnormalities observed in individuals with Down syndrome. Central to this relationship is how the redox state of the cell is affected and its consequences to neural function and integrity.