Immunity, inflammation and disease · 2025
IGF2BP2 Regulates the Progression of Alzheimer's Disease Through m6A-Mediated NLRP3 Inflammasome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jingrui Wu, Haihui Yang, Jinjin Yan, Le Fang
Аннотация
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.
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.