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Proteasomal function is impaired in substantia nigra in Parkinson's disease
McNaught KS, Jenner P.. Neuroscience letters, 2001-01-01
Topic: Brain proteins, microglia and lab models
The accumulation of alpha-synuclein, ubiquitin and other proteins in Lewy bodies in degenerating dopaminergic neurones in substantia nigra in idiopathic Parkinson's disease (PD) suggest that inhibition of normal/abnormal protein degradation may contribute to neuronal death. We now show for the first time that the chymotrypsin- (39%), trypsin- (42%) and postacidic-like (33%) hydrolysing activities of 20/26S proteasome are impaired in substantia nigra in PD. Proteasome inhibition does not appear to result from drug treatment since high concentrations of L-3,4-dihydroxyphenylalanine had no effect on enzymatic activity in vitro. These observations provide the first direct evidence that inhibition of the ubiquitin-proteasome pathway leading to altered protein handling and Lewy body formation may be responsible for degeneration of the nigrostriatal pathway in idiopathic PD.
Key findings
- The accumulation of alpha-synuclein, ubiquitin and other proteins in Lewy bodies in degenerating dopaminergic neurones in substantia nigra in idiopathic Parkinson's disease (PD) suggest that inhibition of normal/abnormal protein degradation may contribute to neuronal death.
- Proteasome inhibition does not appear to result from drug treatment since high concentrations of L-3,4-dihydroxyphenylalanine had no effect on enzymatic activity in vitro.
Why it matters
In brain tissue from people with Parkinson's disease, three proteasome activities were reduced in the substantia nigra, and the drug L-dopa did not cause this reduction in vitro. This supports a role for impaired protein breakdown in Parkinson's disease but does not test a treatment.
Study details
- Evidence strengthLow
How this study scored 47/100
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 (Neuroscience letters) |
| Journal's citation record | 3 / 4 | Neuroscience Letters: journal h-index 267 (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 | 2001 — 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 652 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.1 citations a year over 27 year(s) since 2001 |
| Impact for its field and year | 5 / 6 | Cited 33.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 38 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Peter Jenner: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | King's College London: institution h-index 1,348 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 11137760) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
McNaught, K. S., & Jenner, P. (2001). Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neuroscience letters. https://doi.org/10.1016/s0304-3940(00)01701-8
Vancouver
McNaught KS, Jenner P. Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neuroscience letters. 2001. doi:10.1016/s0304-3940(00)01701-8. PMID: 11137760.
BibTeX
@article{mcnaught2001-11137760,
author = {McNaught, K. S. and Jenner, P.},
title = {{Proteasomal function is impaired in substantia nigra in Parkinson's disease}},
journal = {Neuroscience letters},
year = {2001},
doi = {10.1016/s0304-3940(00)01701-8},
pmid = {11137760},
url = {https://doi.org/10.1016/s0304-3940(00)01701-8}
}
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