Aluminum impairs cognitive function by activating DDX3X-NLRP3-mediated pyroptosis signaling pathway
Cerebral Cortex
0301 basic medicine
0303 health sciences
Inflammasomes
Blotting, Western
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
3. Good health
DEAD-box RNA Helicases
Mice, Inbred C57BL
Mice
03 medical and health sciences
Cognition
Hindlimb Suspension
Microscopy, Electron, Transmission
Blood-Brain Barrier
Morris Water Maze Test
NLR Family, Pyrin Domain-Containing 3 Protein
Pyroptosis
Aluminum Chloride
Animals
Aluminum
Signal Transduction
DOI:
10.1016/j.fct.2021.112591
Publication Date:
2021-10-04T17:14:51Z
AUTHORS (8)
ABSTRACT
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.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.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.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).
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