Therapeutic effects of telomerase-derived peptide GV1001 in experimental autoimmune encephalomyelitis: inhibiting neuroinflammation and promoting remyelination

GV1001, a peptide derived from human telomerase reverse transcriptase, exhibits anti-cancer and anti-inflammatory actions, yet its impact on experimental autoimmune encephalomyelitis (EAE)—an established mouse model of multiple sclerosis—remains unknown. This study assessed the therapeutic potential and mechanism of GV1001 in EAE. Subcutaneous administration of GV1001 reduced clinical scores, inflammatory cytokine transcripts, and spinal cord pathology in EAE mice. Spinal cord RNA-seq showed that GV1001 suppressed immune and neuroinflammatory genes, particularly in microglia. Experiments in cultured mouse and human glia cells identified microglia as the principal cellular target. Mechanistically, GV1001 increased the NF-?B antagonist PRMT1 and boosted microglial insulin-like growth factor-1, promoting oligodendrocyte progenitor cell survival and maturation. Co-culture assays confirmed that GV1001 blunts microglial neurotoxicity and facilitates remyelination during inflammation. Collectively, the data indicate that GV1001 modulates microglial activity to attenuate neuroinflammation and foster spinal cord repair, underscoring its promise as a multitarget therapy for inflammatory demyelinating diseases such as multiple sclerosis. Overall design: RNA-seq profiling of spinal cords from naïve control, EAE, and EAE treated with GV1001 mice

GV1001是源自人端粒酶逆转录酶（human telomerase reverse transcriptase）的肽段，具备抗肿瘤与抗炎活性，但其对实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis, EAE）——一种公认的多发性硬化（multiple sclerosis）小鼠模型——的影响尚不明确。本研究评估了GV1001在EAE模型中的治疗潜力与作用机制。对EAE小鼠皮下给予GV1001，可降低其临床评分、炎性细胞因子转录本水平，并改善脊髓病理损伤。脊髓RNA-seq分析显示，GV1001抑制了免疫与神经炎性基因的表达，尤以小胶质细胞（microglia）中的抑制效应最为显著。通过小鼠与人类胶质细胞（glia）的体外培养实验，研究人员确认小胶质细胞是GV1001的主要作用靶点。从机制上来看，GV1001可上调核因子-κB（NF-κB）拮抗剂蛋白精氨酸甲基转移酶1（PRMT1）的表达，并促进小胶质细胞分泌胰岛素样生长因子-1（insulin-like growth factor-1, IGF-1），进而推动少突胶质细胞前体细胞的存活与成熟。共培养实验证实，GV1001可抑制炎症状态下小胶质细胞的神经毒性，并促进髓鞘再生。综上，本研究数据表明，GV1001可通过调控小胶质细胞活性以减轻神经炎症、促进脊髓修复，凸显其作为多发性硬化等炎性脱髓鞘疾病多靶点治疗药物的应用前景。实验整体设计：对空白对照小鼠、EAE模型小鼠及GV1001治疗的EAE小鼠的脊髓组织开展RNA-seq转录组分析。