Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy.

[]

Dentatorubral-pallidoluysian atrophy (DRPLA ) is one of the CAG-repeat diseases , and is classified into juvenile and early adult types showing progressive myoclonus epilepsy (PME ) in addition to late adult type . We immunohistochemically examined accumulation of oxidative products and expression of superoxide dismutase (SOD ) in autopsy cases of DRPLA . Oxidative products to nucleosides , 8 -hydroxy-2 '-deoxyguanosine and 8 -hydroxyguanosine , were accumulated in the lenticulate nucleus predominantly in DRPLA cases having PME . Neuronal accumulation of 4 -hydroxy nonenal , a reactive lipid aldehyde , was found in the hippocampus , globus pallidus and cerebellar dentate nucleus in adult DRPLA cases and controls . Cytoplasmic immunoreactivity for Cu /ZnSOD was reduced in the external segment of globus pallidus , dentate nucleus and cerebellar cortex in DRPLA cases . Mitochondrial immunoreactivity for MnSOD was reduced in the lenticulate nucleus and cerebellum in DRPLA cases having PME . Some DRPLA cases showed reduced immunoreactivity for MnSOD in the cerebral cortex . Coexistence of reduced SOD expression and polyglutamine was observed in a few cases . It has been discussed in Huntington 's disease that expanded polyglutamine can lead to oxidative neurodegeneration . It is likely that oxidative stress can be involved in DRPLA , although relationship with expanded polyglutamine remains to be elusive .