机构：[1]Department of Geriatrics, the Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan, China.[2]Department of Orthopedics, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, Yunnan, China.骨科外科科室[3]Department of Neurology, the Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan, China.
Alzheimer's disease (AD) is neurodegenerative disease common in the elderly, whose pathological
mechanism is the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain.
Pyroptosis is a programmed cell death mediated by Gasdermin protein. After the activation of
inflammasomes, the cleaved caspase⁃ 1/4/5/11 activates GSDMD, which promotes the release of
inflammatory substances and eventually causes cell swelling and death. Pyroptosis caused by
inflammasomes plays a role in AD. However, the specific regulatory mechanism of pyroptosis in
AD still needs more experimental studies. To further study the effects of NLRP1-induced
pyroptosis on AD, miR-181c-5p, which could targeted bind to NLRP1, was knocked down or
overexpression in HT22 cells to detect cell apoptosis with Tunel assay, the expression of
inflammasome-related proteins with Western blot and the content of inflammatory factors with
ELISA. miR-181c-5p was overexpressed in AD model mice to detect the learning and cognitive
ability with morris water maze testing and the expression of inflammasoma-related proteins with
Western blot. The results showed that miR-181c-5p mimic attenuated Aβ1-42-induced neuronal
pyroptosis in HT22 cells, while up-regulation of NLRP1 aggravated neuronal pyroptosis in HT22
cells. In mice, miR-181c-5p agomir attenuated neuronal pyroptosis in both hippocampal and
cortical tissues, and miR-181c-5p antagomir improved neuronal pyroptosis and cognitive
impairment through NLRP1. Therefore, the study suggests that miR-181c-5p can alleviated AD
process by targeted downregulation of NLRP1, which is expected to be a target site for AD
treatment.
基金：
1. Applied Basic Research Joint Project Fund of Department of Science and Technology of
Yunnan Province and Kunming Medical University (No. 202001AY070001-260, No.
202101AY070001-120, No. 202201AY070001-188).
2. Science and Technology Project of Kunming Medical and Health Commission (Thousand
Project) (No. 2019-03-07-003).
3. Medical Reserve Talents Training Program of Yunnan Health Commission (No. H-2019041).
4. Yunnan Province Clinical Center for Bone and joint Diseases (No. ZX2019-03-04).
5. Yunnan Health Training Program of High-level Talents (No. H-2019012).
6. Special Fund Project of Yunnan Orthopedics and Sports Medicine Rehabilitation Clinical
Medical Research Center (No.202102AA310008)
第一作者机构：[1]Department of Geriatrics, the Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan, China.
通讯作者：
通讯机构：[2]Department of Orthopedics, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, Yunnan, China.[3]Department of Neurology, the Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan, China.
推荐引用方式(GB/T 7714)：
Tingting Wang,Qionghua Long,Yang Hu,et al.miR-181c-5p suppresses neuronal pyroptosis via NLRP1 in Alzheimer's disease[J].Behavioural Brain Research.2023,447:114387.doi:10.1016/j.bbr.2023.114387.
APA：
Tingting Wang,Qionghua Long,Yang Hu,Yongli Yang,Xingguo Li&Huan Wei.(2023).miR-181c-5p suppresses neuronal pyroptosis via NLRP1 in Alzheimer's disease.Behavioural Brain Research,447,
MLA：
Tingting Wang,et al."miR-181c-5p suppresses neuronal pyroptosis via NLRP1 in Alzheimer's disease".Behavioural Brain Research 447.(2023):114387
