Alpha-synuclein is a protein implicated in Parkinson's disease and thought to be one of the main pathological drivers in the disease, although it remains unclear how this protein elicits its neurotoxic effects. Recent findings indicate that the assembly of toxic oligomeric species of alpha-synuclein may be one of the key processes for the pathology and spread of the disease. The absence of a sensitive in situ detection method has hindered the study of these oligomeric species and the role they play in the human brain until recently. In this review, we assess the evidence for the toxicity and prion-like activity of oligomeric forms of alpha-synuclein and discuss the advances in our understanding of the role of alpha-synuclein in Parkinson's disease that may be brought about by the specific and sensitive detection of distinct oligomeric species in post-mortem patient brain. Finally, we discuss current approaches being taken to therapeutically target alpha-synuclein oligomers and their implications.

中文翻译：

---

α-突触核蛋白低聚物：新的希望。

α-突触核蛋白是一种与帕金森氏病有关的蛋白，尽管它尚不清楚该蛋白如何引起其神经毒性作用，但仍被认为是该疾病的主要病理驱动因素之一。最近的发现表明，α-突触核蛋白的有毒寡聚体的组装可能是该疾病的病理学和传播的关键过程之一。缺乏灵敏的原位检测方法阻碍了对这些寡聚物种及其在人脑中的作用的研究，直到最近。在这篇综述中，我们评估了α-突触核蛋白的寡聚形式的毒性和病毒样活性的证据，并讨论了我们对α-突触核蛋白在帕金森病中的作用的理解方面的进展。死后患者大脑中不同寡聚物种的特异性和灵敏检测可能引起这种疾病。最后，我们讨论了治疗性靶向α-突触核蛋白寡聚体的当前方法及其含义。