IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome
ABSTRACT Background Recent studies show that N6‐methyladenosine (m6A) plays an important role in the pathogenesis of the Alzheimer's disease (AD), while the mechanisms involved were studied insufficiently. Aims The present study aimed to explore the effect of human insulin‐like growth factor 2...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.70121 |
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| Summary: | ABSTRACT Background Recent studies show that N6‐methyladenosine (m6A) plays an important role in the pathogenesis of the Alzheimer's disease (AD), while the mechanisms involved were studied insufficiently. Aims The present study aimed to explore the effect of human insulin‐like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2), one of the m6A‐binding proteins on the progression of AD. Materials & Methods The mRNA and protein expression level were determined using RT‐qPCR and western blot, respectively. MTT assay was carried out to evaluate cell viability. The content of ROS, antioxidant enzymes, IL‐1β and pyroptosis, as well as m6A contents were determined using relative commercial kit. The AD models were built using Aβ1‐42 ‐stimulated hippocampal neuron in vitro and AD mice in vivo. Results Our results showed that IGF2BP2 was significantly upregulated in the Aβ1‐42 ‐stimulated hippocampal neuron. IGF2BP2 inhibition reversed the decreased cell viability and the increased cell apoptosis induced by Aβ1‐42. IGF2BP2 siRNA transfection alleviated Aβ1‐42 induced pyroptosis and pyroptosis‐related proteins upregulation. we also found that IGF2BP2 inhibition downregulated the expression of NLRP3 through m6A methylation. Furthermore, overexpression of NLRP3 partly reversed the effect of IGF2BP2 inhibition on Aβ1‐42 ‐induced hippocampal neuron injury. In addition, IGF2BP2 improved cognitive function and alleviated Aβ1‐42 neuronal injury in vivo. Conclusion Knockdown of IGF2BP2 inhibit neuronal damage and pyroptosis in the hippocampus cells, and improve cognitive function in AD partly through m6A‐mediated NLRP3 inflammasome. |
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| ISSN: | 2050-4527 |