Down's syndrome (trisomy 21) brain tissue is considered to be susceptible to oxidative injury, mainly because its increased Cu/Zn-superoxide dismutase (SOD1) activity is not followed by an adaptive rise in hydrogen peroxide metabolizing enzymes.
Cu,Zn superoxide dismutase (SOD-1) and glutathione peroxidase (GSHPx) activities were significantly elevated (1.39-fold and 1.24-fold, respectively) in DS individuals without AD.
A child with characteristic clinical features of Down's syndrome and raised red cell SOD-1 activity was found to have, in addition to a single chromosome 21, a reverse dicentric tandem translocation of two No 21s with dual NORs and C band regions.
A speculative hypothesis about a gene dosage effect of Cu/Zn-superoxide dismutase in preventing toxic radical formation in the substantia nigra of DS patients is presented.
Because both IfRec and SOD-1 map to mouse chromosome 16, it will now be possible to use mice trisomic for this chromosome to determine whether certain aspects of the Down syndrome phenotype in man are caused by an altered dosage of IfRec and SOD-1.
DRG neurons which possessed additional copies of the gene for human superoxide dismutase-1 (SOD), a gene from the Down syndrome region of chromosome 21, were compared to normal neurons.
In this regard, beta amyloid precursor protein (APP), CuZn superoxide dismutase (SOD1) and S100beta have been implicated in causing apoptosis, a mechanism thought to be responsible for neuronal loss in DS, in one way or another.
In this review we will highlight studies which support a key role for SOD1 and APP in the pathogenesis of neural abnormalities observed in individuals with Down syndrome.
Increased SOD-1 levels in patients with DS may reflect the overexpression by the trisomic state, as a response to the oxidative stress, as has been proposed in DS by several authors.
It has been suggested that overexpression of copper-zinc superoxide dismutase (SOD-1) in DS may be involved in some of the abnormalities observed, mainly neurodegenerative and immunopathological processes.
Mutations in the genes Minibrain and SOD1 have been implicated in the development of learning defects in Down syndrome and many new genes from human chromosome 21 are being cloned, which should result in the genesis of other models that phenocopy one or more pathologies of the syndrome.
Our findings suggest that genes on the trisomic Ts1Cje segment other than APP and SOD1 can cause oxidative stress, mitochondrial dysfunction and hyperphosphorylation of tau, all of which may play critical roles in the pathogenesis of mental retardation in DS.
The erythrocyte superoxide dismutase-1 (SOD-1) was found to be normal, and so we conclude that SOD-1 excess is not necessarily observed in patients with Down's syndrome caused by partial 21 trisomy.
The gene locus for human cytoplasmic superoxide dismutase (SOD-1; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is located in or near a region of chromosome 21 known to be involved in Down syndrome.