Parkinson's disease (PD) is a progressive neurodegenerative disease highlighted by a marked loss of dopaminergic cell loss and motor disturbances. Currently, there are no drugs that slow the progression of the disease. A myriad of factors have been implicated in the pathogenesis and progression of PD including neuroinflammation. Although anti-inflammatory agents are being evaluated as potential disease-modifying therapies for PD, none has proven effective to date, suggesting that new and novel targets are needed. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been shown to reduce inflammation in astrocytes and to be increased in post-mortem PD brain samples. Here we show that transgenic overexpression of GPNMB protects against dopaminergic neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropridine mouse model of Parkinson's disease. Furthermore, GPNMB overexpression reduces gliosis and prevented microglial morphological changes following MPTP treatment compared with wild-type MPTP-treated mice. Additionally, recombinant GPNMB attenuates LPS-induced inflammation in primary mouse microglia. These results suggest a neuroprotective and anti-inflammatory role for GPNMB and warrant further investigation for GPNMB as a novel therapy for PD.

中文翻译：

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GPNMB的转基因过表达保护免受MPTP诱导的神经变性。

帕金森氏病（PD）是一种进行性神经退行性疾病，突出表现为多巴胺能细胞损失明显减少和运动障碍。当前，没有药物可以减慢疾病的进展。PD的发病机理和进展包括神经发炎，涉及多种因素。尽管抗炎药正在被评估为PD的潜在疾病缓解疗法，但迄今为止尚未证明有效，表明需要新的靶标。糖蛋白非转移性黑色素瘤蛋白B（GPNMB）是一种跨膜糖蛋白，最近被证明可减少星形胶质细胞的炎症，并在验尸后的PD脑样本中增加。在这里，我们显示GPNMB的转基因过度表达可防止多巴胺能神经退行性疾病在1-甲基-4-苯基-1,2,3，帕金森氏病的6-四氢吡啶小鼠模型。此外，与野生型MPTP处理的小鼠相比，MPPN处理后GPNMB的过表达减少了神经胶质细胞增生，并防止了小胶质细胞形态变化。此外，重组GPNMB可减轻LPS诱导的原发性小鼠小胶质细胞的炎症。这些结果表明对GPNMB具有神经保护和抗炎作用，并且有必要进一步研究GPNMB作为PD的新疗法。