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The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity
Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farer M, Wolozin B.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000-08-01
Topic: Brain proteins, microglia and lab models
Parkinson's disease (PD) is the most common motor disorder affecting the elderly. PD is characterized by the formation of Lewy bodies and death of dopaminergic neurons. The mechanisms underlying PD are unknown, but the discoveries that mutations in alpha-synuclein can cause familial PD and that alpha-synuclein accumulates in Lewy bodies suggest that alpha-synuclein participates in the pathophysiology of PD. Using human BE-M17 neuroblastoma cells overexpressing wild-type, A53T, or A30P alpha-synuclein, we now show that iron and free radical generators, such as dopamine or hydrogen peroxide, stimulate the production of intracellular aggregates that contain alpha-synuclein and ubiquitin. The aggregates can be identified by immunocytochemistry, electron microscopy, or the histochemical stain thioflavine S. The amount of aggregation occurring in the cells is dependent on the amount of alpha-synuclein expressed and the type of alpha-synuclein expressed, with the amount of alpha-synuclein aggregation following a rank order of A53T > A30P > wild-type > untransfected. In addition to stimulating aggregate formation, alpha-synuclein also appears to induce toxicity. BE-M17 neuroblastoma cells overexpressing alpha-synuclein show up to a fourfold increase in vulnerability to toxicity induced by iron. The vulnerability follows the same rank order as for aggregation. These data raise the possibility that alpha-synuclein acts in concert with iron and dopamine to induce formation of Lewy body pathology in PD and cell death in PD.
Key findings
- The mechanisms underlying PD are unknown, but the discoveries that mutations in alpha-synuclein can cause familial PD and that alpha-synuclein accumulates in Lewy bodies suggest that alpha-synuclein participates in the pathophysiology of PD.
Why it matters
In human neuroblastoma cells, iron and free radical generators stimulated formation of alpha-synuclein- and ubiquitin-containing aggregates, and cells overexpressing alpha-synuclein were more vulnerable to iron-induced toxicity. This is a cell study of Parkinson disease mechanisms and does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2000 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 467 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.7 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 4 / 6 | Cited 15.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 33 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Benjamin L. Wolozin: h-index 77 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Mayo Clinic in Florida: institution h-index 681 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10934254) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.20-16-06048.2000
- PubMed: 10934254
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Ostrerova-Golts, N., Petrucelli, L., Hardy, J., Lee, J. M., Farer, M., & Wolozin, B. (2000). The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.20-16-06048.2000
Vancouver
Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farer M, Wolozin B. The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2000. doi:10.1523/jneurosci.20-16-06048.2000. PMID: 10934254.
BibTeX
@article{ostrerovagolts2000-10934254,
author = {Ostrerova-Golts, N. and Petrucelli, L. and Hardy, J. and Lee, J. M. and Farer, M. and Wolozin, B.},
title = {{The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2000},
doi = {10.1523/jneurosci.20-16-06048.2000},
pmid = {10934254},
url = {https://doi.org/10.1523/jneurosci.20-16-06048.2000}
}
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