Abstract
Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are caused by a genetic
defect of nucleotide excision repair mechanisms, showing cutaneous hypersensitivity
to sunlight and progressive neurological disturbances. The cause of neurological abnormalities
has yet to be clarified and fundamental treatments have never been established in
both disorders. In order to investigate neurodegeneration of XPA and CS, we immunohistochemically
examined deposition of oxidative stress-related materials of nucleotides and expression
of two types of superoxide dismutase (SOD) in the brains from autopsy cases of XPA
and CS. Cases of XPA but not CS demonstrated nuclear deposition of 8-hydroxy-2′-deoxyguanosine
and cytoplasmic deposition of 8-hydroxyguanosine, being speculated as oxidative stress-related
materials of DNA and RNA, respectively, in the globus pallidus. Four of five XPA cases
exhibited reduced neuronal immunoreactivity for Cu/ZnSOD in the cerebral and cerebellar
corteces in addition to the basal ganglia, and two XPA cases showed reduced immunoreactivity
for MnSOD in the brain regions examined. In contrast, five CS cases demonstrated comparatively
preserved immunoreactivity for Cu/ZnSOD and MnSOD. Both XPA and CS cases showed increased
cytoplasmic immunoreactivity for Cu/ZnSOD and/or MnSOD in the microglial cells in
the cerebral and cerebellar white matters. These findings suggest that oxidative damage
to nucleotides and disturbed SOD expression can be involved in neurodegeneration in
XPA but not CS.
Keywords
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Article info
Publication history
Accepted:
April 2,
2004
Received in revised form:
March 10,
2004
Received:
January 27,
2004
Identification
Copyright
© 2004 Elsevier B.V. Published by Elsevier Inc. All rights reserved.