代谢紊乱药物抑制小胶质细胞介导的神经炎症中的 CXCL10 分泌。
Mitigation of CXCL10 secretion by metabolic disorder drugs in microglial-mediated neuroinflammation.
机构信息
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
出版信息
J Neuroimmunol. 2024 Jun 15;391:578364. doi: 10.1016/j.jneuroim.2024.578364. Epub 2024 May 3.
Metabolic disorders are associated with several neurodegenerative diseases. We previously identified C-X-C motif chemokine ligand 10 (CXCL10), also known as interferon gamma-induced protein 10 (IP-10), as a major contributor to the type I interferon response in microglial-mediated neuroinflammation. Therefore, we hypothesized FDA-approved metabolic disorder drugs that attenuate CXCL10 secretion may be repurposed as a treatment for neurodegenerative diseases. Screening, dose curves, and cytotoxicity assays in LPS-stimulated microglia yielded treprostinil (hypertension), pitavastatin (hyperlipidemia), and eplerenone (hypertension) as candidates that significantly reduced CXCL10 secretion (in addition to other pro-inflammatory mediators) without impacting cell viability. Altogether, these data suggest metabolic disorder drugs that attenuate CXCL10 as potential treatments for neurodegenerative disease through mitigating microglial-mediated neuroinflammation.
代谢紊乱与多种神经退行性疾病有关。我们之前发现 C-X-C 基序趋化因子配体 10（CXCL10），也称为干扰素γ诱导蛋白 10（IP-10），是小胶质细胞介导的神经炎症中 I 型干扰素反应的主要贡献者。因此，我们假设减轻 CXCL10 分泌的已批准用于治疗代谢紊乱的药物可能被重新用于治疗神经退行性疾病。在 LPS 刺激的小胶质细胞中进行的筛选、剂量曲线和细胞毒性测定显示，曲前列尼尔（高血压）、匹伐他汀（高血脂）和依普利酮（高血压）是显著减少 CXCL10 分泌（除其他促炎介质外）而不影响细胞活力的候选药物。总之，这些数据表明，通过减轻小胶质细胞介导的神经炎症，减轻 CXCL10 的代谢紊乱药物可能成为治疗神经退行性疾病的潜在治疗方法。
Zotero 插件