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The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats
Abstract
The etiology and pathogenesis of Parkinson's disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days. Then, rotational behavior, the number of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and the mRNA and protein expression levels of NLRP3 inflammasome components were measured 14 days after the microinjection setup was established. Results showed that high mRNA and protein expression levels of NLRP3 inflammasome components were observed in the injected side of the LPS- and 6-OHDA-induced PD rats; Ac-YVAD-CMK inhibited the mRNA and protein expression of NLRP3 inflammasome components in both LPS- and 6-OHDA-induced PD rats. Moreover, the number of rotations was significantly decreased, and the number of DA neurons in the SNc improved. Our data indicate that the NLRP3 inflammasome participates in the pathogenesis of PD and that inhibiting the downstream pathway of the NLRP3/caspase-1/IL-1β axis can alleviate the occurrence of PD symptoms, providing a new basis for the prevention and treatment of PD.
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“Injection of the caspase-1 inhibitor Ac-YVAD-CMK was shown to reduce the expression of NLRP inflammasome signaling proteins and improve the number of dopaminergic neurons in LPS- and 6-hydroxydopamine-induced PD in rats (242).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [242]
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Metadata
- Authors
- Mao, Z., Liu, C., Ji, S., Yang, Q., Ye, H., Han, H., & Xue, Z.
- Affiliations
- Tongji Hospital (CN)
- Guangzhou First People's Hospital (CN)
- Corresponding author
- Xue, Zheng
- Venue
- Neurochemical Research
- Published
- 2017-02-28
- Volume
- 42
- Issue
- 4
- Pages
- 1104-1115
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2592822773
- Cited by
- 155
- References
- 52
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 16 · 2023: 21 · 2022: 20 · 2021: 27 · 2020: 26 · 2019: 12 · 2018: 12 · 2017: 4
- FWCI
- 10.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Hubei Province
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, NLRP3 inflammasome, caspase-1, IL-1β, neuroinflammation, lipopolysaccharide-induced neurotoxicity, 6-hydroxydopamine, substantia nigra pars compacta, dopaminergic neurons, Ac-YVAD-cmk, rotational behavior, rat model
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Male, Random Allocation, Oxidopamine, Rats, Sprague-Dawley, Parkinsonian Disorders, Rats, Inflammasomes
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