The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
Caspase-1 causes truncation and aggregation of the Parkinson’s disease-associated protein α-synuclein
Open accessAbstract
Significance: The aggregation of α-synuclein (aSyn) is a pathological hallmark of Parkinson’s disease. Here we show that the enzymatic component of the innate inflammation system, known as caspase-1, hydrolyzes aSyn, rendering it aggregation-prone.
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“This could create an inflammatory environment that promotes α-synuclein expression, misfolding, and aggregation which subsequently triggers further gut dysbiosis, inflammation, and luminal hyperpermeability initiating a viscous positive feedback cycle [113–117].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [114]
In the citing paper
“injection of endotoxin into mice induces α-synuclein production and aggregation, as well as loss of dopaminergic neurons in the substantia nigra.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [71]
In the citing paper
“Endotoxin may also promote the production or aggregation of amyloid β [66–68], tau [68, 69] and α-synuclein [70, 71].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [71]
In the citing paper
“Endotoxin increases α-synuclein production by macrophages [100] and drives α-synuclein fibrillization [70, 71].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [71]
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Metadata
- Authors
- Wang, W., Nguyen, L. T. T., Burlak, C., Chegini, F., Guo, F., Chataway, T., Ju, S., Fisher, O. S., Miller, D. W., Datta, D., Wu, F., Wu, C.-X., Landeru, A., Wells, J. A., Cookson, M. R., Boxer, M. B., Thomas, C. J., Gai, W. P., Ringe, D., Petsko, G. A., & Hoang, Q. Q.
- Affiliations
- Indiana University Indianapolis (US)
- University of Minnesota (US)
- Flinders University (AU)
- Brandeis University (US)
- National Institutes of Health (US)
- University of California, San Francisco (US)
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-08
- Volume
- 113
- Issue
- 34
- Pages
- 9587-9592
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5003239
- OpenAlex
- W2503377259
- Cited by
- 270
- References
- 52
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 22 · 2023: 31 · 2022: 39 · 2021: 41 · 2020: 28 · 2019: 28 · 2018: 32 · 2017: 13 · 2016: 2
- FWCI
- 18.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- DH | National Institute for Health Research (1R21NS079881-01, 5R01GM111639)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, Parkinson's disease, caspase-1, protein truncation, protein aggregation, Lewy bodies, inflammasome, neuroinflammation, neurotoxicity, sporadic Parkinson's disease
- MeSH terms
- Alum Compounds, Cell Survival, Dipeptides, Gene Expression Regulation, Humans, Lipopolysaccharides, Neurons, Nigericin, Signal Transduction, Lewy Bodies, Caspase 1, Vitamin K 3, RNA, Small Interfering, Cell Line, Tumor, alpha-Synuclein, Interleukin-1beta, Inflammasomes, para-Aminobenzoates, Protein Aggregates
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