Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239.
Department of Behavioral and Systems Neuroscience, Oregon Health and Science University, Portland, OR 97239.
Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2306731120. doi: 10.1073/pnas.2306731120. Epub 2023 Jul 31.
Amyotrophic lateral sclerosis (ALS) is a fatal disease affecting upper and lower motor neurons. Microglia directly interact with motor neurons and participate in the progression of ALS. Single-cell mass cytometry (CyTOF) analysis revealed prominent expression of α5 integrin in microglia and macrophages in a superoxide dismutase-1 G93A mouse model of ALS (SOD1). In postmortem tissues from ALS patients with various clinical ALS phenotypes and disease duration, α5 integrin is prominent in motor pathways of the central and peripheral nervous system and in perivascular zones associated with the blood-brain barrier. In SOD1 mice, administration of a monoclonal antibody against α5 integrin increased survival compared to an isotype control and improved motor function on behavioral testing. Together, these findings in mice and in humans suggest that α5 integrin is a potential therapeutic target in ALS.
肌萎缩侧索硬化症（ALS）是一种致命疾病，影响上下运动神经元。小胶质细胞直接与运动神经元相互作用，并参与 ALS 的进展。单细胞质量细胞术（CyTOF）分析显示，在超氧化物歧化酶 1 G93A 肌萎缩侧索硬化症（SOD1）小鼠模型中，α5 整联蛋白在小胶质细胞和巨噬细胞中表达明显。在具有不同临床肌萎缩侧索硬化症表型和疾病持续时间的肌萎缩侧索硬化症患者的死后组织中，α5 整联蛋白在中枢和周围神经系统的运动通路以及与血脑屏障相关的血管周围区域中表现明显。在 SOD1 小鼠中，与同种型对照相比，针对 α5 整联蛋白的单克隆抗体的给药增加了存活并改善了行为测试中的运动功能。这些在小鼠和人类中的发现表明，α5 整联蛋白是 ALS 的潜在治疗靶标。
