Cited by 156Parkinson's Disease Mechanisms and TreatmentsInflammasome and immune disordersNeuroinflammation and Neurodegeneration Mechanisms

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The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats

Mao, Zhijuan, Liu, Chanchan, Ji, Suqiong, Yang, Qingmei, Ye, Hongxiang, Han, Haiyan, Xue, Zheng·2017·Neurochemical Research

DOI 10.1007/s11064-017-2185-0

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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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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
ORCID: Ji, Suqiong
Yang, Qingmei
Han, Haiyan
Xue, Zheng
Venue: Neurochemical Research
Publisher: Springer Science and Business Media LLC
Published: 2017-02-28
Volume: 42
Issue: 4
Pages: 1104-1115
ISSN: 0364-3190 (ISSN-L)
1573-6903
DOI: 10.1007/s11064-017-2185-0
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
Licence: www.springer.com/tdm (unspecified)
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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The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats

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