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Updated: Dec 25, 2025
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Laquinimod inhibits MMP+ induced NLRP3 inflammasome activation in human neuronal cells
Xue Zhang1, Jianing Jin1, Anmu Xie1
1Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
Abstract:
Objective: Nod-like receptor protein 3 (NLRP3) inflammasome plays anessentialrole in neuroinflammation in the Parkinson's disease (PD) progression. Laquinimodis an immunomodulator that is clinically used for the treatment of multiple sclerosis. This study aims to investigate whether laquinimod possessesa protective effect against MPP+-induced NLRP3 activation.Materials and methods: In a variety of tests on human SH-SY5Y neuronal cells, 1-methyl-4-phenyl Pyridine (MPP+) was used to mimic the microenvironment of PD. Activation of NLRP3 inflammasome was measured by western blot analysis and enzyme linked immunosorbent assay (ELISA).Results: Laquinimod had a significant protective impact against MPP+-induced neurotoxicity. Our results demonstrate that laquinimod prevented MPP+-induced reduction of cell proliferation, the release of lactate dehydrogenase (LDH), and apoptosis. Importantly, treatment with laquinimod significantly inhibited the activation of the NLRP3 inflammasome by reducing the levels of its components, including NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved caspase 1 (P10). Consistently, laquinimod prevented MPP+-induced secretions of interleukin 1β (IL-1β) and interleukin-18 (IL-18). Additionally, laquinimod also reduced the expression of other related factors, such as intracellular reactive oxygen species (ROS), NADPH oxidase 4 (NOX-4), thioredoxin-interacting protein (TxNIP). Furthermore, laquinimod prevented the reduction of sirtuin 1 (SIRT1) from MPP+ stimulation. Inhibition of SIRT1 abolished the protective effects of laquinimod against the activation of the NLRP3 inflammasome, suggesting the involvement of SIRT1 in this process.Conclusion: These findings suggest that laquinimod treatment might be a possible therapeutic strategy for neuroinflammation in PD.
Insights
Laquinimod protects against Parkinson's disease neurotoxicity by inhibiting NLRP3 inflammasome activation. This immunomodulator reduces neuroinflammation and cell damage, suggesting a potential therapeutic role in PD treatment.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Neuroinflammation, driven by the NLRP3 inflammasome, is critical in Parkinson's disease (PD) progression.
- Laquinimod, an immunomodulator used for multiple sclerosis, is explored for its neuroprotective potential.
Purpose of the Study:
- To investigate the protective effects of laquinimod against MPP+-induced neurotoxicity and NLRP3 inflammasome activation in a cellular model of Parkinson's disease.
Main Methods:
- Human SH-SY5Y neuronal cells were treated with 1-methyl-4-phenyl pyridine (MPP+) to mimic PD neuroenvironment.
- NLRP3 inflammasome activation was assessed using Western blot and ELISA.
- Cell proliferation, LDH release, apoptosis, and inflammatory cytokine secretion were measured.
Main Results:
- Laquinimod significantly protected against MPP+-induced neurotoxicity, reducing cell death and apoptosis.
- Laquinimod inhibited NLRP3 inflammasome activation by decreasing NLRP3, ASC, and cleaved caspase-1 levels.
- It also reduced IL-1β, IL-18, ROS, NOX-4, and TxNIP, while preserving SIRT1 levels.
Conclusions:
- Laquinimod demonstrates significant neuroprotective effects against MPP+-induced damage and NLRP3 inflammasome activation.
- The findings suggest laquinimod's therapeutic potential for managing neuroinflammation in Parkinson's disease, potentially via SIRT1 pathways.
