Cited by 429Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNuclear Receptors and Signaling

Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro

Hashimoto, Makoto, Hsu, Leigh J., Xia, Yu, Takeda, Ayako, Sisk, Abbyann, Sundsmo, Mary, Masliah, Eliezer·1999·NeuroReport

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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Crossref · 10.1097/00001756-199903170-00011

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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)”

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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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