After Alzheimer's disease, Parkinson's disease is the most frequent neurodegenerative disorder. Although numerous treatments have been developed to control the disease symptomatology, with some successes, an efficacious therapy affecting the causes of PD is still a goal to pursue. The genetic evidence and the identification of α-synuclein as the main component of intracellular Lewy bodies, the neuropathological hallmark of PD and related disorders, have changed the approach to these disorders. More recently, the detrimental role of α-synuclein has been further extended to explain the wide spread of cerebral pathology through its oligomers. To emphasize the central pathogenic role of these soluble aggregates, we have defined synucleinopathies and other neurodegenerative disorders associated with protein misfolding as oligomeropathies. Another common element in the pathogenesis of oligomeropathies is the role played by inflammation, both at the peripheral and cerebral levels. In the brain parenchyma, inflammatory reaction has been considered an obvious consequence of neuronal degeneration, but recent observations indicate a direct contribution of glial alteration in the early phase of the disease. Furthermore, systemic inflammation also influences the development of neuronal dysfunction caused by specific elements, β amyloid, α-synuclein, tau or prion. However, each disorder has its own specific pathological process and within the same pathological condition, it is possible to find inter-individual differences. This heterogeneity might explain the difficulties developing efficacious therapeutic approaches, even though the possibility of intervention is supported by robust biological evidence. We have recently demonstrated that peripheral inflammation can amplify the neuronal dysfunction induced by α-synuclein oligomers and the neuropathological consequences observed in a Parkinson's disease model. In both cases, activation of microglia was incremented by the “double hit” process, compared to the single treatment. In contrast, astrocyte activation was attenuated and these cells appeared damaged when chronic inflammation was combined with α-synuclein exposure. This evidence might indicate a more specific anti-inflammatory strategy rather than the generic anti-inflammatory treatment.

在阿尔茨海默病之后，帕金森病是最常见的神经退行性疾病。尽管已经开发了多种治疗方法来控制疾病症状，并取得了一些成功，但影响 PD 病因的有效疗法仍然是一个追求的目标。α-突触核蛋白作为细胞内路易小体的主要成分（PD 和相关疾病的神经病理学标志）的遗传证据和鉴定已经改变了对这些疾病的研究方法。最近，α-突触核蛋白的有害作用进一步扩展到通过其寡聚体来解释脑病理学的广泛传播。为了强调这些可溶性聚集体的主要致病作用，我们将突触核蛋白病和其他与蛋白质错误折叠相关的神经退行性疾病定义为寡聚病. 寡聚体病发病机制中的另一个常见因素是炎症在外周和大脑水平上的作用。在脑实质中，炎症反应被认为是神经元变性的明显后果，但最近的观察表明，在疾病的早期阶段，神经胶质改变有直接作用。此外，全身炎症也会影响由特定元素、β 淀粉样蛋白、α-突触核蛋白、tau 或朊病毒引起的神经元功能障碍的发展。然而，每种疾病都有其特定的病理过程，在相同的病理条件下，可能会发现个体差异。这种异质性可能解释了开发有效治疗方法的困难，即使干预的可能性得到了强有力的生物学证据的支持。我们最近证明，外周炎症可以放大由 α-突触核蛋白寡聚体诱导的神经元功能障碍，以及在帕金森病模型中观察到的神经病理学后果。在这两种情况下，与单次治疗相比，“双重打击”过程增加了小胶质细胞的激活。相比之下，当慢性炎症与 α-突触核蛋白暴露相结合时，星形胶质细胞的活化减弱，这些细胞似乎受损。这一证据可能表明一种更具体的抗炎策略，而不是一般的抗炎治疗。我们最近证明，外周炎症可以放大由 α-突触核蛋白寡聚体诱导的神经元功能障碍，以及在帕金森病模型中观察到的神经病理学后果。在这两种情况下，与单次治疗相比，“双重打击”过程增加了小胶质细胞的激活。相比之下，当慢性炎症与 α-突触核蛋白暴露相结合时，星形胶质细胞的活化减弱，这些细胞似乎受损。这一证据可能表明一种更具体的抗炎策略，而不是一般的抗炎治疗。我们最近证明，外周炎症可以放大由 α-突触核蛋白寡聚体诱导的神经元功能障碍，以及在帕金森病模型中观察到的神经病理学后果。在这两种情况下，与单次治疗相比，“双重打击”过程增加了小胶质细胞的激活。相比之下，当慢性炎症与 α-突触核蛋白暴露相结合时，星形胶质细胞的活化减弱，这些细胞似乎受损。这一证据可能表明一种更具体的抗炎策略，而不是一般的抗炎治疗。当慢性炎症与α-突触核蛋白暴露相结合时，星形胶质细胞的活化减弱，这些细胞似乎受损。这一证据可能表明一种更具体的抗炎策略，而不是一般的抗炎治疗。当慢性炎症与α-突触核蛋白暴露相结合时，星形胶质细胞的活化减弱，这些细胞似乎受损。这一证据可能表明一种更具体的抗炎策略，而不是一般的抗炎治疗。