Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
J Neural Transm (Vienna). 2010 Aug;117(8):1019-25. doi: 10.1007/s00702-010-0431-6. Epub 2010 Jun 12.
One common feature of neurodegenerative diseases is neuroinflammation. In the case of Parkinson's disease (PD), neuroinflammation appears early and persists throughout the disease course. The principal cellular mediator of brain inflammation is the resident microglia which share many features with related hematopoietically derived macrophages. Microglia can become activated by misfolded proteins including the PD relevant example, alpha-synuclein, a presynaptic protein. When activated, microglia release pro-inflammatory diffusible mediators that promote dysfunction and contribute to the death of the PD vulnerable dopaminergic neurons in the midbrain. Recently, the orphan nuclear receptor Nurr1, well known as a critical determinant in dopaminergic neuron maturation, has been ascribed two new properties. First, it promotes the production and release of the neuropeptide vasoactive intestinal peptide that functions both to stimulate dopaminergic neuron survival and inhibit neuroinflammation. Second, Nurr1 suppresses the expression and release of pro-inflammatory cytokines in glial cells. Herein, we discuss these new findings in context of strategies to attenuate neuroinflammation in PD.
神经退行性疾病的一个共同特征是神经炎症。在帕金森病（PD）中，神经炎症似乎很早就出现了，并贯穿整个疾病过程。大脑炎症的主要细胞介质是驻留的小胶质细胞，它与相关的造血衍生的巨噬细胞有许多共同特征。小胶质细胞可以被包括 PD 相关的α-突触核蛋白在内的错误折叠蛋白激活，α-突触核蛋白是一种突触前蛋白。当被激活时，小胶质细胞释放促炎的可扩散介质，促进功能障碍，并导致中脑 PD 易损的多巴胺能神经元死亡。最近，孤儿核受体 Nurr1 作为多巴胺能神经元成熟的关键决定因素，被赋予了两个新的特性。首先，它促进神经肽血管活性肠肽的产生和释放，该肽具有刺激多巴胺能神经元存活和抑制神经炎症的双重作用。其次，Nurr1 抑制神经胶质细胞中促炎细胞因子的表达和释放。在此，我们将这些新发现置于减轻 PD 中神经炎症的策略背景下进行讨论。
