Romero-Ramos Marina, von Euler Chelpin Marianne, Sanchez-Guajardo Vanesa
CNS disease modeling group; Department of Biomedicine; Aarhus University; Aarhus, Denmark; NEURODIN; Department of Biomedicine; Aarhus University; Aarhus, Denmark.
CNS disease modeling group; Department of Biomedicine; Aarhus University; Aarhus, Denmark; NEURODIN; Department of Biomedicine; Aarhus University; Aarhus, Denmark; Neuroimmunology of Degenerative Diseases group; Department of Biomedicine; Aarhus University; Aarhus, Denmark.
Hum Vaccin Immunother. 2014;10(4):852-67. doi: 10.4161/hv.28578. Epub 2014 Mar 26.
Parkinson disease is the second most common neurodegenerative disease in the world, but there is currently no available cure for it. Current treatments only alleviate some of the symptoms for a few years, but they become ineffective in the long run and do not stop the disease. Therefore it is of outmost importance to develop therapeutic strategies that can prevent, stop, or cure Parkinson disease. A very promising target for these therapies is the peripheral immune system due to its probable involvement in the disease and its potential as a tool to modulate neuroinflammation. But for such strategies to be successful, we need to understand the particular state of the peripheral immune system during Parkinson disease in order to avoid its weaknesses. In this review we examine the available data regarding how dopamine regulates the peripheral immune system and how this regulation is affected in Parkinson disease; the specific cytokine profiles observed during disease progression and the alterations documented to date in patients' peripheral blood mononuclear cells. We also review the different strategies used in Parkinson disease animal models to modulate the adaptive immune response to salvage dopaminergic neurons from cell death. After analyzing the evidence, we hypothesize the need to prime the immune system to restore natural tolerance against α-synuclein in Parkinson disease, including at the same time B and T cells, so that T cells can reprogram microglia activation to a beneficial pattern and B cell/IgG can help neurons cope with the pathological forms of α-synuclein.
帕金森病是世界上第二常见的神经退行性疾病，但目前尚无治愈方法。目前的治疗方法只能在几年内缓解部分症状，但从长远来看会失效，且无法阻止疾病进展。因此，开发能够预防、阻止或治愈帕金森病的治疗策略至关重要。外周免疫系统因其可能参与该疾病以及作为调节神经炎症的工具的潜力，成为这些治疗方法非常有前景的靶点。但要使这些策略成功，我们需要了解帕金森病期间外周免疫系统的特殊状态，以避免其弱点。在本综述中，我们研究了关于多巴胺如何调节外周免疫系统以及这种调节在帕金森病中如何受到影响的现有数据；疾病进展过程中观察到的特定细胞因子谱以及迄今为止患者外周血单核细胞中记录的变化。我们还回顾了帕金森病动物模型中用于调节适应性免疫反应以挽救多巴胺能神经元免于细胞死亡的不同策略。在分析证据后，我们推测需要激发免疫系统以恢复帕金森病中对α-突触核蛋白的天然耐受性，包括同时激发B细胞和T细胞，以便T细胞能够将小胶质细胞激活重编程为有益模式，并且B细胞/IgG能够帮助神经元应对α-突触核蛋白的病理形式。
