DOI: 10.1002/ame2.12297
Neutralizing peripheral circulating IL1β slows the progression of ALS in a lentivirus- infected OPTN E478G mouse model
Wen-Bao Hu
Xin Wang
Zhi-Lin Pang
Ran Duan
Chun-Gu Hong
Zheng-Zhao Liu
Xiangya Hospital,Central South University,Changsha,China
摘要：Background : Amyotrophic lateral sclerosis (ALS) is irreversible and fatal within 3– 5 years, with limited options for treatment. It is imperative to develop a symptom- based treatment that may increase the survival of ALS patients and improve their quality of life. Inflammation status, especially elevated interleukin 1β (IL1β), has been reported to play a critical role in ALS progression. Our study determined that neutralizing circulating IL1β slows down the progression of ALS in an ALS mouse model. Methods : The ALS mouse model was developed by microinjection of lentivirus- carrying OPTN E478G (optineurin, a mutation from ALS patients) into the intra- motor cortex of mice. Peripheral circulating IL1β was neutralized by injecting anti- IL1β an-tibody into the tail vein. Enzyme-l inked immunosorbent assay (ELISA) and real- time polymerase chain reaction (RT- PCR) were carried out to determine the protein and gene expression levels of IL1β. TUNEL assay was used to assess the neural cell death. Immunofluorescent staining of MAP2 and CASP3 was accomplished to evaluate neuronal cell apoptosis. Glial fibrillary acidic protein staining was performed to ana-lyze the number of astrocytes. Rotarod test, grip strength test, balance beam test, and footprint test were conducted to assess the locomotive function after anti- IL1β treatment. Results : The model revealed that neuroinflammation contributes to ALS progression. ALS mice exhibited elevated neuroinflammation and IL1β secretion. After anti- IL1β treatment, ALS mice revealed decreased neural cell death and astrogliosis and gained improved muscle strength and motor ability. Conclusions : Blocking IL1β is a promising strategy to slow down the progression of ALS.
机标关键词：optnmousemodelcirculatinginfectedlentivirus-neutralizingperipheral
论文发表日期：2023-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 18-25 )
英文信息