Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH⁺) and microglia markers (Iba-1⁺; CD68⁺) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68⁺/ Iba-1⁺ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

炎症是神经退行性疾病的主要方面，在帕金森病 (PD) 动物模型中进行的实验研究表明，持续的神经炎症会加剧黑质纹状体变性途径。小胶质细胞在神经炎症中的核心作用已被研究为潜在的 PD 神经保护药物的靶点，例如非甾体抗炎药 (NSAID) 和调节小胶质细胞活化和迁移的基质金属蛋白酶 (MMP) 抑制剂。本研究的目的是研究亚氨基糖 1-脱氧野尻霉素 (1-DNJ) 的神经保护反应，并将其与布洛芬联合治疗的效果进行比较。MPTP 治疗的小鼠口服布洛芬和/或 1-DNJ 1。使用露天试验来评估行为变化。⁺ ) 和小胶质细胞标记物 (Iba-1 ⁺ ; CD68 ⁺ ) 用于研究黑质致密部 (SNpc) 中的神经元完整性和小胶质细胞激活。通过qPCR分析促炎细胞因子TNF-α和IL-6。单独使用 1-DNJ 或布洛芬治疗并不能减少 MPTP 中毒引起的损伤。然而，1-DNJ 和布洛芬联合治疗可防止中脑多巴胺能神经元的丢失，减少 CD68 ⁺ / Iba-1 ^{+ 的数量}细胞、小胶质细胞/神经元相互作用和促炎细胞因子，与 MPTP 治疗的动物相比，改善了行为变化。总之，这些数据表明，MMPs 抑制剂（1-DNJ）加抗炎药（布洛芬）的联合治疗具有神经保护作用，可用于未来的治疗干预。

MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）是一种促毒剂，在穿过血脑屏障后，被星形胶质细胞 MAO-B 代谢为 MPDP+，这是一种吡啶中间体，再经过两次- 电子氧化产生有毒代谢物 MPP+（甲基-苯基四氢吡啶鎓），然后通过中脑多巴胺转运蛋白选择性地转运到黑质神经元中。在这项研究中，我们证明了 MPTP 诱导了小鼠多巴胺能神经元的死亡、小胶质细胞增生、胶质瘤增加、运动障碍和神经炎症，这些都被 1-脱氧野尻霉素和布洛芬联合治疗所抑制。