| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
To detemine oxcidative damage involvenent in non-hereditary neurodegenerative diseases, we performed immunohistochemical, immunoelectron microscopic (IEM), immunoblot and enzyme-linked tmmunosorbent assay (ELISA) analyzes of oxidative modification products of nucleic acids, lipids and proteins in the central nervous systetem of patients with sporadic amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), Parkinson s disease (PD) and progressive supranuclear palsy (PSP). In the ALS spinal cords, 8-hydroxy-2 -deoxyguanosine (OHdG), 4-hydroxy-2-nonenal-histidine (HNEH), crotonaldehyde-lysine (CRAL), N-*(carboxytmethyl)lysine (CM1), and pentosidine accumulated in neurons and astrocytes. In the PD brains, HNEH accumulated in neurons and astrocytes, and CRAL accumulated in these cells and Lewy bodies. In the MSA brains, HNEH, CRAL and CML accumulated in neurons, astrocytes and glial cytoplasmic inclusions. In the PSP brains, HNTEH, CRAL and CML accumulated in neurons, astrocytes and neurofibrillary tangles. IEM depicted the localization of OHdG in the cell nuclei and the localization of the examined prodcuts other than OHdG in the cytoplasms. Immunoblots disclosed smear-like immunoreactive patterns of these products in the ALS spinal cords, suggesting that a variety of oxidative modification products are formed in this disease. ELISA could not detect any of the products because of the difficulty of solubulization of these products. Our results indicate that oxidative damage is implicated in the pathomechanisms of ALS, MSA, PD and PSP, and that combinations of deposited oxidative modification products varied among these diseases.
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