Aluminum impairs cognitive function by activating DDX3X-NLRP3-mediated pyroptosis signaling pathway
Link: https://pubmed.ncbi.nlm.nih.gov/34614429/
2021 Nov;157:112591. doi: 10.1016/j.fct.2021.112591. Epub 2021 Oct 3.
Wudi Hao 1, Chenyu Hao 1, Chengrong Wu 1, Yuqing Xu 1, Shengwen Wu 1, Xiaobo Lu 1, Jinghua Yang 1, Cuihong Jin 2
- PMID: 34614429 DOI: 10.1016/j.fct.2021.112591
Abstract
Introduction: Aluminum is a kind of chemical contaminants in food which can induce neurotoxicity. Aluminum exposure is closely related to neurodegenerative diseases (ND), in which neuroinflammation might involve. However, the molecular mechanism of aluminum-induced neuroinflammation through pyroptosis is not fully clarified yet.
Material and methods: The mice model of subacute exposure to aluminum chloride (AlCl3) was established. BV2 microglia cells was treated with AlCl3 in vitro. Resveratrol (Rsv) was adopted as intervention agent.
Results: Our results showed that aluminum induced cognitive impairment, destroying blood brain barrier (BBB), and causing nerve injury in mice. Meanwhile, aluminum could stimulate nucleotide oligomerization domain-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome assembly and activate caspase-1 (CASP1), inducing gasdermin D (GSDMD)-mediated pyroptosis signaling, releasing cytokines IL-1β and IL-18, further promoting the activation of glial cells to magnify neuroinflammatory response. Moreover, DEAD-box helicase 3 X-linked (DDX3X) and stress granule RasGAP SH3-domain-binding protein 1 (G3BP1) both participated in neuroinflammation induced by aluminum. When co-treated with Rsv, these injuries were alleviated to some extent.
Conclusion: Aluminum exposure could induce nerve cell pyroptosis and neuroinflammation by DDX3X-NLRP3 inflammasome signaling pathway, which could be rescued via Rsv activating sirtuin 1 (SIRT1).
Keywords: Aluminum exposure; Inflammasome assembly; Neuroinflammation; Pyroptosis; Resveratrol.
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