Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro
Abstract
The precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein), found in Lewy bodies of Parkinson's disease (PD), is a presynaptic protein genetically linked to some familial types PD. Mechanisms of abnormal NACP/alpha-synuclein aggregation in neurodegenerative diseases are unclear. Since oxidative stress might play a role in PD pathogenesis, we investigated the role of iron and peroxide in NACP/alpha-synuclein aggregation. Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Ferrous ion was not effective by itself, but it potentially aggregated NACP/alpha-synuclein in the presence of hydrogen peroxide. NACP/ alpha-synuclein aggregates displayed strong thioflavine-S and congo-red reactivity, reminiscent of amyloid. This study suggests that NACP/alpha-synuclein aggregation might be closely related to oxidative reactions which may play a critical role in neurodegeneration in disorders with Lewy bodies.
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Regulation of ferritin synthesis by iron is mainly due to posttranscriptional regulation through binding of IRP1 and IRP2 to an IRE in the 5′ UTR of ferritin mRNA.
“The regulation of ferritin synthesis by iron is mainly due to posttranscriptional regulation (107, 129, 262) through the binding of IRP1 and IRP2 to an IRE located in the 5′ UTR of ferritin mRNA (41)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [129]
Cites
Identification of two distinct synucleins from human brain
Jakes, R., Spillantini, M. G., & Goedert, M. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00395-5 · Cited by 1,080 · see citing works
Pathology and Biology of the Lewy Body
Pollanen, M. S., Dickson, D. W., & Bergeron, C. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199305000-00001 · Cited by 396 · see citing works
The Role of Iron in Beta Amyloid Toxicity
Schubert, D. A., & Chevion, M. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2678 · Cited by 159 · see citing works
Ueda, K., Saitoh, T., & Mori, H. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2816 · Cited by 130 · see citing works
Peripheral Nervous System-specific Genes Identified by Subtractive cDNA Cloning
Akopian, A. N., & Wood, J. N. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.21264 · Cited by 100 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845 · see citing works
Chung, K. K. K., Zhang, Y., Lim, K. L., Tanaka, Y., Huang, H., Gao, J., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2001) · Nature Medicine · doi:10.1038/nm1001-1144 · Cited by 750 · see citing works
Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease
Zucca, F. A., Segura-Aguilar, J., Ferrari, E., Muñoz, P., Paris, I., Sulzer, D., Sarna, T., Casella, L., & Zecca, L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.09.012 · Cited by 659 · see citing works
Masliah, E., Rockenstein, E., Veinbergs, I., Sagara, Y., Mallory, M., Hashimoto, M., & Mucke, L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211412398 · Cited by 607 · see citing works
Self-citationIntracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
β-Synuclein Inhibits α-Synuclein Aggregation
Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M., & Masliah, E. (2001) · Neuron · doi:10.1016/s0896-6273(01)00462-7 · Cited by 398 · see citing works
Self-citationIron Toxicity in Diseases of Aging: Alzheimer's Disease, Parkinson's Disease and Atherosclerosis
Altamura, S., & Muckenthaler, M. U. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1010 · Cited by 369 · see citing works
Brain iron pathways and their relevance to Parkinson's disease
Berg, D., Gerlach, M., Youdim, M. B. H., Double, K. L., Zecca, L., Riederer, P., & Becker, G. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00608.x · Cited by 362 · see citing works
Alpha‐Synuclein as a Biomarker for Parkinson's Disease
Atik, A., Stewart, T., & Zhang, J. (2016) · Brain Pathology · doi:10.1111/bpa.12370 · Cited by 311 · see citing works
Evidence of Oxidative Stress in the Neocortex in Incidental Lewy Body Disease
Dalfó, E., Portero-Otín, M., Ayala, V., Martínez, A., Pamplona, R., & Ferrer, I. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000179050.54522.5a · Cited by 261 · see citing works
Shults, C. W., Rockenstein, E., Crews, L., Adame, A., Mante, M., Larrea, G., Hashimoto, M., Song, D., Iwatsubo, T., Tsuboi, K., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3527-05.2005 · Cited by 254 · see citing works
Self-citationProtein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus
Ashraf, G., Greig, N., Khan, T., Hassan, I., Tabrez, S., Shakil, S., Sheikh, I., Zaidi, S., Akram, M., Jabir, N., et al. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140917095514 · Cited by 236 · see citing works
The role of free radicals in the aging brain and Parkinson’s Disease: Convergence and parallelism
Kumar, H., Lim, H.-W., More, S. V., Kim, B.-W., Koppula, S., Kim, I. S., & Choi, D.-K. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130810478 · Cited by 212 · see citing works
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Kaur, D., & Andersen, J. (2004) · Ageing Research Reviews · doi:10.1016/j.arr.2004.01.003 · Cited by 123 · see citing works
Schröder, N., Figueiredo, L. S., & de Lima, M. N. M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121996 · Cited by 113 · see citing works
Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease
Hochstrasser, H., Bauer, P., Walter, U., Behnke, S., Spiegel, J., Csoti, I., Zeiler, B., Bornemann, A., Pahnke, J., Becker, G., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000144276.29988.c3 · Cited by 111 · see citing works
Pathogenic Mechanisms of Neurodegeneration in Parkinson Disease
Mullin, S., & Schapira, A. H. V. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2014.09.010 · Cited by 108 · see citing works
Glial cell death induced by overexpression of α‐synuclein
Stefanova, N., Klimaschewski, L., Poewe, W., Wenning, G. K., & Reindl, M. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.1171 · Cited by 93 · see citing works
Functional relevance of ceruloplasmin mutations in Parkinson's Disease
Hochstrasser, H., Tomiuk, J., Walter, U., Behnke, S., Spiegel, J., Krüger, R., Becker, G., Riess, O., & Berg, D. (2005) · The FASEB Journal · doi:10.1096/fj.04-3486fje · Cited by 87 · see citing works
Takeda, A., Hashimoto, M., Mallory, M., Sundsumo, M., Hansen, L., & Masliah, E. (2000) · Acta Neuropathologica · doi:10.1007/pl00007441 · Cited by 83 · see citing works
Self-citationProbiotics and the Treatment of Parkinson's Disease: An Update
Mirzaei, H., Sedighi, S., Kouchaki, E., Barati, E., Dadgostar, E., Aschner, M., & Tamtaji, O. R. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01128-w · Cited by 57 · see citing works
Bencsik, A., Muselli, L., Leboidre, M., Lakhdar, L., & Baron, T. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000137 · Cited by 48 · see citing works
Ironing out Parkinson's disease: is therapeutic treatment with iron chelators a real possibility?
Kaur, D., & Andersen, J. K. (2002) · Aging Cell · doi:10.1046/j.1474-9728.2002.00001.x · Cited by 44 · see citing works
- Authors
- Hashimoto, M., Hsu, L. J., Xia, Y., Takeda, A., Sisk, A., Sundsmo, M., & Masliah, E.
- Affiliations
- University of California San Diego (US)
- Venue
- NeuroReport
- Published
- 1999-03
- Volume
- 10
- Issue
- 4
- Pages
- 717-721
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W2086857730
- Cited by
- 429
- References
- 5
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 13 · 2021: 11 · 2020: 15 · 2019: 12 · 2018: 16 · 2017: 11 · 2016: 16 · 2015: 11 · 2014: 12 · 2013: 10 · 2012: 18
- FWCI
- 21.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG10689, AG05131, R01AG010689, P50AG005131)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, oxidative stress, protein aggregation, amyloid-like aggregates, Parkinson's disease, Lewy bodies, iron, iron(III), hydrogen peroxide, deferoxamine, iron chelation, neurodegeneration, thioflavine S, Congo red
- MeSH terms
- Alzheimer Disease, Amyloid, Catalysis, Chlorides, Ferric Compounds, Ferrous Compounds, Humans, Nerve Tissue Proteins, Oxidation-Reduction, Recombinant Proteins, Oxidative Stress, Synucleins, alpha-Synuclein, beta-Synuclein
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