The DOI matches its Crossref record; 94 of the 96 references it cites were found in a registry or an index.
Proteolytic stress: A unifying concept for the etiopathogenesis of Parkinson’s disease
Abstract
The etiopathogenesis of Parkinson's disease (PD) has been elusive. Recently, several lines of evidence have converged to suggest that defects in the ubiquitin-proteasome system and proteolytic stress underlie nigral pathology in both familial and sporadic forms of the illness. In support of this concept, mutations in alpha-synuclein that cause the protein to misfold and resist proteasomal degradation cause familial PD. Similarly, mutations in two enzymes involved in the normal function of the ubiquitin-proteasome system, parkin and ubiquitin C-terminal hydrolase L1, are also associated with hereditary PD. Furthermore, structural and function defects in 26/20S proteasomes with accumulation and aggregation of potentially cytotoxic abnormal proteins have been identified in the substantia nigra pars compacta of patients with sporadic PD. Thus, a defect in protein handling appears to be a common factor in sporadic and the various familial forms of PD. This hypothesis may also account for the vulnerability of the substantia nigra pars compacta in PD, why the disorder is age related, and the nature of the Lewy body. It has also facilitated the development of experimental models that recapitulate the behavioral and pathological features of PD, and hopefully will lead to the development of novel neuroprotective therapies for the disorder.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Insight into the reduction of proteasomal activity in PD [94,95,96] further supports the evidence of the accumulation of pSer40-TH to form inclusion bodies in PD patients [71].”
From Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia (2020) · cites this paper as [96]
In the citing paper
“Failure of the ubiquitin-proteasome system is implicated in the pathogenesis of both sporadic and familial PD [22,23,24,94,95,96].”
From Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia (2020) · cites this paper as [96]
Citations
Cites
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R. S., Sherer, T., MacKenzie, G. M., Garcia‐Osuna, M., Panov, A. V., & Greenamyre, J. T. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,770
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
Gibb, W. R., & Lees, A. J. (1988) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.51.6.745 · Cited by 3,481
Mechanisms Underlying Ubiquitination
Pickart, C. M. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.503 · Cited by 3,184
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 2,868
Impairment of the Ubiquitin-Proteasome System by Protein Aggregation
Bence, N., Sampat, R. M., & Kopito, R. R. (2001) · Science · doi:10.1126/science.292.5521.1552 · Cited by 2,209
A Drosophila model of Parkinson's disease
Feany, M. Β., & Bender, W. W. (2000) · Nature · doi:10.1038/35006074 · Cited by 2,156
Aggresomes: A Cellular Response to Misfolded Proteins
Johnston, J. A., Ward, C. L., & Kopito, R. R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.7.1883 · Cited by 2,148
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024
Flagged first, then by citations
2 of the 96 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Lee, 2001, J Biol Chem, 27, 27
Cited by
Sorted by citations
Items 201–203 of 203
Fan, T., Wei, C., Chen, W., Li, S., Wang, J., Lu, Y., & Renshi, X. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1915475
Derkinderen, P., & Damier, P. (2011) · Elsevier eBooks · doi:10.1016/b978-2-294-71153-4.00002-0
Metadata
- Authors
- McNaught, K. S. P., & Olanow, C. W.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Olanow, C. Warren
- ORCID
- Olanow, C. Warren
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2003
- Volume
- 53
- Issue
- S3
- Pages
- S73-S86
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2135387829
- Cited by
- 203
- References
- 96
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 7 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns033772-09)
- National Institute of Neurological Disorders and Stroke (NS 33772)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- Parkinson's disease, ubiquitin-proteasome system, alpha-synuclein, Parkin, UCHL1, substantia nigra pars compacta, Lewy bodies, familial Parkinson's disease, sporadic Parkinson's disease, protein aggregation, neuroprotection
- MeSH terms
- Cysteine Endopeptidases, Humans, Ligases, Multienzyme Complexes, Nerve Degeneration, Nerve Tissue Proteins, Parkinson Disease, Peptide Hydrolases, Substantia Nigra, Thiolester Hydrolases, Lewy Bodies, Point Mutation, Ubiquitin Thiolesterase, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex, Synucleins, alpha-Synuclein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
