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...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.70121 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832087064496046080 |
|---|---|
| author | Wu Jingrui Yang Haihui Yan Jinjin Fang Le |
| author_facet | Wu Jingrui Yang Haihui Yan Jinjin Fang Le |
| author_sort | Wu Jingrui |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-db09c9171ad94717bb2f754abc9c3a62 |
| institution | Kabale University |
| issn | 2050-4527 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj-art-db09c9171ad94717bb2f754abc9c3a622025-02-06T07:50:38ZengWileyImmunity, Inflammation and Disease2050-45272025-01-01131n/an/a10.1002/iid3.70121IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 InflammasomeWu Jingrui0Yang Haihui1Yan Jinjin2Fang Le3College of Medical Technology Xi'an Medical College Xi'an Shaanxi ChinaCollege of Medical Technology Xi'an Medical College Xi'an Shaanxi ChinaDepatment of Medical Technology Huyi District Xi'an Shaanxi ChinaDepartment of Clinical Laboratory Norinco General Hospital Xi'an Shaanxi ChinaABSTRACT 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.https://doi.org/10.1002/iid3.70121Alzheimer's diseaseAβN6‐methyladenosinepyroptosis |
| spellingShingle | Wu Jingrui Yang Haihui Yan Jinjin Fang Le IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome Immunity, Inflammation and Disease Alzheimer's disease Aβ N6‐methyladenosine pyroptosis |
| title | IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome |
| title_full | IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome |
| title_fullStr | IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome |
| title_full_unstemmed | IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome |
| title_short | IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A‐Mediated NLRP3 Inflammasome |
| title_sort | igf2bp2 regulates the progression of alzheimer s disease through m6a mediated nlrp3 inflammasome |
| topic | Alzheimer's disease Aβ N6‐methyladenosine pyroptosis |
| url | https://doi.org/10.1002/iid3.70121 |
| work_keys_str_mv | AT wujingrui igf2bp2regulatestheprogressionofalzheimersdiseasethroughm6amediatednlrp3inflammasome AT yanghaihui igf2bp2regulatestheprogressionofalzheimersdiseasethroughm6amediatednlrp3inflammasome AT yanjinjin igf2bp2regulatestheprogressionofalzheimersdiseasethroughm6amediatednlrp3inflammasome AT fangle igf2bp2regulatestheprogressionofalzheimersdiseasethroughm6amediatednlrp3inflammasome |