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Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective
Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM.. The Journal of biological chemistry, 2003-11-19
Topic: Brain proteins, microglia and lab models
Lewy bodies (LBs), which are the hallmark pathologic features of Parkinson's disease and of dementia with LBs, have several morphologic and molecular similarities to aggresomes. Whether such cytoplasmic inclusions contribute to neuronal death or protect cells from the toxic effects of misfolded proteins remains controversial. In this report, the role of aggresomes in cell viability was addressed in the context of over-expressing alpha-synuclein and its interacting partner synphilin-1 using engineered 293T cells. Inhibition of proteasome activity elicited the formation of juxtanuclear aggregates with characteristics of aggresomes including immunoreactivity for vimentin, gamma-tubulin, ubiquitin, proteasome subunit, and hsp70. As expected from the properties of aggresomes, the microtubule disrupting agents, vinblastin and nocodazole, markedly prevented the formation of these inclusions. Similar to LBs, the phosphorylated form of alpha-synuclein co-localized in these synphilin-1-containing aggresomes. Although the caspase inhibitor z-VAD-fmk significantly reduced the number of apoptotic cells, it had no impact on the percentage of aggresome-positive cells. Finally, quantitative analysis revealed aggresomes in 60% of nonapoptotic cells but only in 10% of apoptotic cells. Additionally, alpha-synuclein-induced apoptosis was not coupled with increased prevalence of aggresome-bearing cells. Taken together, these observations indicate a disconnection between aggresome formation and apoptosis, and support a protective role for these inclusions from the toxicity associated with the combined over-expression of alpha-synuclein and synphilin-1.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tanaka, M., Kim, Y. M., Lee, G., Junn, E., Iwatsubo, T., & Mouradian, M. M. (2004). Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m310994200
Vancouver
Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM. Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. The Journal of biological chemistry. 2004. doi:10.1074/jbc.m310994200. PMID: 14627698.
BibTeX
@article{tanaka2004-14627698,
author = {Tanaka, M. and Kim, Y. M. and Lee, G. and Junn, E. and Iwatsubo, T. and Mouradian, M. M.},
title = {{Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective}},
journal = {The Journal of biological chemistry},
year = {2004},
doi = {10.1074/jbc.m310994200},
pmid = {14627698},
url = {https://doi.org/10.1074/jbc.m310994200}
}
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.
Key findings
- Although the caspase inhibitor z-VAD-fmk significantly reduced the number of apoptotic cells, it had no impact on the percentage of aggresome-positive cells.
- Finally, quantitative analysis revealed aggresomes in 60% of nonapoptotic cells but only in 10% of apoptotic cells.
- Taken together, these observations indicate a disconnection between aggresome formation and apoptosis, and support a protective role for these inclusions from the toxicity associated with the combined over-expression of alpha-synuclein and synphilin-1.
Why it matters
In this cell study, aggresomes formed by alpha-synuclein and synphilin-1 were found in 60% of nonapoptotic cells but only 10% of apoptotic cells, indicating a disconnection between aggresome formation and apoptosis. The authors support a protective role for these inclusions from the toxicity associated with combined over-expression of alpha-synuclein and synphilin-1.
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Study details
- Evidence strengthLow
How this study scored 50/100
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 biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 2004 — 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 423 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.6 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 5 / 6 | Cited 23.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 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 M. Maral Mouradian: h-index 69 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14627698) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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Read the original
- DOI: 10.1074/jbc.m310994200
- PubMed: 14627698
- Original source →
- Free full text: Journal of Biological Chemistry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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