MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson’s disease
Open accessAbstract
BACKGROUND: α-Synuclein (α-Syn), a pathological hallmark of Parkinson's disease (PD), has been recognized to induce the production of interleukin-1β in a process that depends, at least in vitro, on nod-like receptor protein 3 (NLRP3) inflammasome in monocytes. However, the role of NLRP3 inflammasome activation in the onset of PD has not yet been fully established. RESULTS: In this study, we showed that NLRP3 inflammasomes were activated in the serum of PD patients and the midbrain of PD model mice. We further clarified that α-syn activated the NLRP3 inflammasome through microglial endocytosis and subsequent lysosomal cathepsin B release. Deficiency of caspase-1, an important component of NLRP3 inflammasome, significantly inhibited α-syn-induced microglia activation and interleukin-1β production, which in turn alleviated the reduction of mesencephalic dopaminergic neurons treated by microglia medium. Specifically, we demonstrated for the first time that Nlrp3 is a target gene of microRNA-7 (miR-7). Transfection of miR-7 inhibited microglial NLRP3 inflammasome activation whereas anti-miR-7 aggravated inflammasome activation in vitro. Notably, stereotactical injection of miR-7 mimics into mouse striatum attenuated dopaminergic neuron degeneration accompanied by the amelioration of microglial activation in MPTP-induced PD model mice. CONCLUSIONS: Our study provides a direct link between miR-7 and NLRP3 inflammasome-mediated neuroinflammation in the pathogenesis of PD. These findings will give us an insight into the potential of miR-7 and NLRP3 inflammasome in terms of opening up novel therapeutic avenues for PD.
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NLRP3 knockdown or knockout reduced neuroinflammation and neurodegeneration in an MPTP-induced PD mouse model.
“NLRP3 knockdown or knockout was also found to reduce neuroinflammation and neurodegeneration in an MPTP-induced PD mouse model.360,361”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [360]
The Results section on miR-7 mimics reports reduced microglial activation and rescued dopaminergic neuron loss in MPTP-treated mice, alongside inhibited NLRP3 inflammasome activation. But the intervention was miR-7 mimics, not NLRP3 knockdown or knockout. The knockout experiment used caspase-1-deficient A53T mice to assess microglial activation, not NLRP3-deficient MPTP mice. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredInhibiting expression of NLRP3 by microRNA ameliorates α-synuclein aggregation and protects dopaminergic neurons against degeneration in a mouse model of PD.
“Inhibiting the expression of NLRP3 by microRNA can ameliorate α-synuclein aggregation and protect dopaminergic neurons against degeneration in a mouse model of PD.360”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [360]
The Results section reports that miR-7 mimics inhibited NLRP3 activation and rescued dopaminergic neuron loss in MPTP-treated mice (page unavailable). The Discussion notes a possible link between reduced miR-7 and increased α-synuclein accumulation, but does not report that the treatment ameliorated α-synuclein aggregation. (LLM, conf=0.88)
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- Authors
- Zhou, Y., Lu, M., Du, R.-H., Qiao, C., Jiang, C.-Y., Zhang, K.-Z., Ding, J.-H., & Hu, G.
- Affiliations
- Nanjing Medical University (CN)
- Nanjing University of Chinese Medicine (CN)
- Corresponding author
- Hu, Gang
- Venue
- Molecular Neurodegeneration
- Published
- 2016-04-16
- Volume
- 11
- Issue
- 1
- Pages
- 28-28
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC4833896
- OpenAlex
- W2340005882
- Cited by
- 455
- References
- 10
- Citations by year
- 2026: 26 · 2025: 38 · 2024: 41 · 2023: 58 · 2022: 54 · 2021: 56 · 2020: 54 · 2019: 50 · 2018: 45 · 2017: 27 · 2016: 6
- FWCI
- 32.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81473196, 81573403)
- Natural Science Foundation of Jiangsu Province (BK20130039)
- the key project of Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (15KJA310002)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Parkinson's disease, microRNA-7, NLRP3 inflammasome, neuroinflammation, alpha-synuclein, IL-1β, caspase-1, microglial activation, dopaminergic neuron loss, MPTP mouse model, cathepsin B, striatum
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Disease Models, Animal, Parkinson Disease, Microglia, Mice, Knockout, MicroRNAs, Inflammasomes, Dopaminergic Neurons
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