Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, China.
CNS Neurosci Ther. 2022 Mar;28(3):422-434. doi: 10.1111/cns.13791. Epub 2022 Jan 5.
Multiple sclerosis (MS) still maintains increasing prevalence and poor prognosis, while glucagon-like peptide-1 receptor (GLP-1R) agonists show excellent neuroprotective capacities recently. Thus, we aim to evaluate whether the GLP-1R agonist liraglutide (Lira) could ameliorate central nervous system demyelination and inflammation.
The therapeutic effect of Lira was tested on experimental autoimmune encephalitis (EAE) in vivo and a microglia cell line BV2 in vitro.
Lira administration could ameliorate the disease score of EAE mice, delay the disease onset, ameliorate pathological demyelination and inflammation score in lumbar spinal cord, reduce pathogenic T helper cell transcription in spleen, restore phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) level, autophagy level, and inhibit pyroptosis-related NLR family, pyrin domain-containing protein 3 (NLRP3) pathway in lumbar spinal cord. Additionally, cell viability test, lactate dehydrogenase release test, and dead/live cell staining test for BV2 cells showed Lira could not salvage BV2 from nigericin-induced pyroptosis significantly.
Lira has anti-inflammation and anti-demyelination effect on EAE mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK pathway, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro. Our study provides Lira as a potential candidate for Multiple Sclerosis treatment.
多发性硬化症（MS）的患病率仍在不断上升，且预后较差，而胰高血糖素样肽-1 受体（GLP-1R）激动剂最近显示出良好的神经保护能力。因此，我们旨在评估 GLP-1R 激动剂利拉鲁肽（Lira）是否可以改善中枢神经系统脱髓鞘和炎症。
在体内实验性自身免疫性脑脊髓炎（EAE）和体外小胶质细胞系 BV2 中测试 Lira 的治疗效果。
Lira 给药可改善 EAE 小鼠的疾病评分，延迟疾病发作，改善腰椎脊髓的病理性脱髓鞘和炎症评分，减少脾脏中致病性辅助性 T 细胞转录，恢复磷酸化腺苷单磷酸激活蛋白激酶（pAMPK）水平、自噬水平，并抑制腰椎脊髓中的 NLR 家族、pyrin 结构域包含蛋白 3（NLRP3）通路。此外，BV2 细胞的细胞活力试验、乳酸脱氢酶释放试验和死活细胞染色试验表明，利拉鲁肽不能显著挽救 Nigericin 诱导的 BV2 细胞发生细胞焦亡。
Lira 对 EAE 小鼠具有抗炎和抗脱髓鞘作用，Lira 在 EAE 模型中的保护作用可能与调节 pAMPK 通路、自噬和 NLRP3 通路有关。然而，Lira 治疗不能显著抑制体外 BV2 细胞的细胞焦亡。我们的研究为 Lira 作为多发性硬化症治疗的潜在候选药物提供了依据。
