The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
RNA Oxidation Is a Prominent Feature of Vulnerable Neurons in Alzheimer’s Disease
Open accessAbstract
In this study we used an in situ approach to identify the oxidized nucleosides 8-hydroxydeoxyguanosine (8OHdG) and 8-hydroxyguanosine (8OHG), markers of oxidative damage to DNA and RNA, respectively, in cases of Alzheimer’s disease (AD). The goal was to determine whether nuclear and mitochondrial DNA as well as RNA is damaged in AD. Immunoreactivity with monoclonal antibodies 1F7 or 15A3 recognizing both 8OHdG and 8OHG was prominent in the cytoplasm and to a lesser extent in the nucleolus and nuclear envelope in neurons within the hippocampus, subiculum, and entorhinal cortex as well as frontal, temporal, and occipital neocortex in cases of AD, whereas similar structures were immunolabeled only faintly in controls. Relative density measurement showed that there was a significant increase (p< 0.0001) in 8OHdG and 8OHG immunoreactivity with 1F7 in cases of AD (n= 22) as compared with senile (n= 13), presenile (n= 10), or young controls (n= 4). Surprisingly, the oxidized nucleoside was associated predominantly with RNA because immunoreaction was diminished greatly by preincubation in RNase but only slightly by DNase. This is the first evidence of increased RNA oxidation restricted to vulnerable neurons in AD. The subcellular localization of damaged RNA showing cytoplasmic predominance is consistent with the hypothesis that mitochondria may be a major source of reactive oxygen species that cause oxidative damage in AD.
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Cites
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Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499
Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease
Mecocci, P., MacGarvey, U., & Beal, M. F. (1994) · Annals of Neurology · doi:10.1002/ana.410360510 · Cited by 1,037
Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., & Beal, M. F. (1993) · Annals of Neurology · doi:10.1002/ana.410340416 · Cited by 757 · cited 3×
“The OD in an area comprising the cytoplasm and nucleus was determined with a Quantimet 570C Image Processing and Analysis System (Leica) linked to a C OHU solid state camera mounted on a Leitz Laborlux 12 M E ST microscope, according to the methods of Masliah et al. (1990) .”
BackgroundMethodResultMitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain
Mecocci, P., Beal, M. F., Cecchetti, R., Polidori, M. C., Cherubini, A., Chionne, F., Avellini, L., Romano, G., & Senin, U. (1997) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815160 · Cited by 215
Neuropil threads of Alzheimer's disease show a marked alteration of the normal cytoskeleton
Perry, G., Kawai, M., Tabaton, M., Onorato, M., Mulvihill, P., Richey, P., Morandi, A., Connolly, J., & Gambetti, P. (1991) · The Journal of Neuroscience · doi:10.1523/jneurosci.11-06-01748.1991 · Cited by 140
Self-citation
Cited by
Oxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383
Oxidative Damage Is the Earliest Event in Alzheimer Disease
Nunomura, A., Perry, G., Aliev, G., Hirai, K., Takeda, A., Balraj, E. K., Jones, P. K., Ghanbari, H., Wataya, T., Shimohama, S., et al. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.8.759 · Cited by 1,885
Self-citationMitochondrial abnormalities in Alzheimer's disease
Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03017.2001 · Cited by 1,367
Self-citationOxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357
Self-citationThe metallobiology of Alzheimer's disease
Bush, A. I. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00067-5 · Cited by 1,315
Metadata
- Authors
- Nunomura, A., Perry, G., Pappolla, M. A., Wade, R., Hirai, K., Chiba, S., & Smith, M. A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-03-15
- Volume
- 19
- Issue
- 6
- Pages
- 1959-1964
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1896970469
- Cited by
- 722
- References
- 7
- FWCI
- 19.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
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