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Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway
Lee HJ, Khoshaghideh F, Patel S, Lee SJ.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004-02-01
Topic: Brain proteins, microglia and lab models
Cytoplasmic deposition of alpha-synuclein aggregates is a common pathological feature of many neurodegenerative diseases. Strong evidence for the causative role of alpha-synuclein in these disorders is provided by genetic linkage between this gene and familial Parkinson's disease and by neurodegeneration in transgenic animals that overexpress this protein. In particular, it has been hypothesized that the accumulation of nonfibrillar oligomers of alpha-synuclein, which serve as intermediates for fibrillar inclusion body formation, causes neurodegeneration. However, little is known about how cells handle potentially toxic protein aggregates. Here we demonstrate that cells are capable of clearing preformed alpha-synuclein aggregates via the lysosomal degradation pathway. Consequently, blocking this pathway causes the accumulation of the aggregates in non-neuronal cells, differentiated neuroblastoma cells, and primary cortical neurons. This aggregate clearance occurs in an aggregation stage-specific manner; oligomeric intermediates are susceptible to clearance, whereas mature fibrillar inclusion bodies are not. Neutralization of the acidic compartments leads to the accumulation of alpha-synuclein aggregates and exacerbates alpha-synuclein toxicity in postmitotic neuronal cells, suggesting that the accumulation of oligomeric intermediates may be an important event leading to alpha-synuclein-mediated cell death. These results suggest that enhancing lysosomal function may be a potential therapeutic strategy to halt or even prevent the pathogenesis of Parkinson's disease and other Lewy body diseases.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lee, H. J., Khoshaghideh, F., Patel, S., & Lee, S. J. (2004). Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.3809-03.2004
Vancouver
Lee HJ, Khoshaghideh F, Patel S, Lee SJ. Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004. doi:10.1523/jneurosci.3809-03.2004. PMID: 14985429.
BibTeX
@article{lee2004-14985429,
author = {Lee, H. J. and Khoshaghideh, F. and Patel, S. and Lee, S. J.},
title = {{Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2004},
doi = {10.1523/jneurosci.3809-03.2004},
pmid = {14985429},
url = {https://doi.org/10.1523/jneurosci.3809-03.2004}
}
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
- Neutralization of the acidic compartments leads to the accumulation of alpha-synuclein aggregates and exacerbates alpha-synuclein toxicity in postmitotic neuronal cells, suggesting that the accumulation of oligomeric intermediates may be an important event leading to alpha-synuclein-mediated cell death.
- These results suggest that enhancing lysosomal function may be a potential therapeutic strategy to halt or even prevent the pathogenesis of Parkinson's disease and other Lewy body diseases.
Why it matters
In cells and neurons, the lysosomal degradation pathway can clear oligomeric alpha-synuclein but not mature fibrillar inclusion bodies, and blocking this pathway worsened alpha-synuclein toxicity. Enhancing lysosomal function is suggested as a possible way to halt or prevent Parkinson's disease and other Lewy body diseases.
Study details
- Evidence strengthLow
How this study scored 48/100
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 | 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 447 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.6 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 71 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Seung‐Jae Lee: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Seoul National University: institution h-index 1,053 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14985429) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.3809-03.2004
- PubMed: 14985429
- 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).
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