| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
UV-damaged-DNA binding protein (UV-DDB) is an intracytoplasmic protein of heterodimer consisting of 127 kDa and 48 kDa, the former of which binds with the cytoplasmic domain of amyloid β protein precursor (APP). In this research project, we immunohistochemically investigated the expression and distribution of UV-DDB in the normal and diseased brains (3 Alzheimer's disease cases, 2 non-dementia autopsy cases) by using the specific polyclonal antibodies (Watanabe T.at al., J.Neurochem. 72, 2, 549-556, 1999). Specific antibodies against β-amyloid protein (βA), choline acetyltransferatse (ChAT), tau, ubiquitin were also applied on the paraformaldehyde-fixed paraffin section of those cases. Expression of each protein was noted on normal nerve cells, degenerating nerve cells, neurofibrillary tangles, and senile plaques in the frontal lobes, cerebral basilar nuclei and hypocampus. ChAT immunohistochemistry was negative in Alzheimer's deisease brain. βA and ubiquitin immunoreactivities were positive in the senile plaques. Particularly the degenerating nerve cells and their processes were immunoreactive with ubiquitin, suggesting the increase of proteosome enzymatic actibity. UV-DDB immunoreactivity was negative in the control brains, but Alzheimer's diseased brains were weakly positive for UV-DDB in degenerating nerve cells, particularly in areas of the diffuse type senile plaques and neurofibrillary tangles in the frontal lobes and hypocampus. Thus, UV-DDB which binds to AP sites of the protein during DNA damage may be expressed in the nuclei of particular degenerating nerve cells for reparative processes
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