Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, 11794-8651, USA.
Sci Rep. 2020 Nov 9;10(1):19333. doi: 10.1038/s41598-020-76383-w.
Multiple sclerosis (MS) is an autoimmune disease characterized by infiltration of peripheral immune cells into the central nervous system, demyelination, and neuronal damage. There is no cure for MS, but available disease-modifying therapies can lessen severity and delay progression. However, current therapies are suboptimal due to adverse effects. Here, we investigate how the FDA-approved antihypertensive drug, guanabenz, which has a favorable safety profile and was recently reported to enhance oligodendrocyte survival, exerts effects on immune cells, specifically microglia and macrophages. We first employed the experimental autoimmune encephalomyelitis (EAE) model and observed pronounced immunomodulation evident by a reduction in pro-inflammatory microglia and macrophages. When guanabenz was administered in the cuprizone model, in which demyelination is less dependent upon immune cells, we did not observe improvements in remyelination, oligodendrocyte numbers, and effects on microglial activation were less dramatic. Thus, guanabenz may be a promising therapeutic to minimize inflammation without exerting severe off-target effects.
多发性硬化症（MS）是一种自身免疫性疾病，其特征是外周免疫细胞浸润中枢神经系统、脱髓鞘和神经元损伤。目前尚无治愈多发性硬化症的方法，但现有的疾病修正疗法可以减轻病情严重程度并延缓疾病进展。然而，由于存在不良反应，目前的治疗方法并不理想。在这里，我们研究了已被 FDA 批准的降压药胍那苄如何发挥作用，该药物具有良好的安全性，最近有报道称其可增强少突胶质细胞的存活。我们首先采用实验性自身免疫性脑脊髓炎（EAE）模型，观察到明显的免疫调节作用，表现为促炎小胶质细胞和巨噬细胞减少。当胍那苄在少突胶质细胞髓鞘溶解模型中被给药时，髓鞘溶解的发生不太依赖于免疫细胞，我们没有观察到髓鞘再生、少突胶质细胞数量的改善，并且对小胶质细胞激活的影响也不那么显著。因此，胍那苄可能是一种很有前途的治疗方法，可以在不产生严重的脱靶效应的情况下最大限度地减少炎症。
