α-Synuclein (αS) aggregation is the main neurological hallmark of a group of debilitating neurodegenerative disorders, collectively referred to as synucleinopathies, of which Parkinson's disease is the most prevalent. αS oligomers formed during the initial stages of aggregation are considered key pathogenic drivers of disease onset and progression, standing as privileged targets for therapeutic intervention and diagnosis. However, the structure of αS oligomers and the mechanistic basis of oligomer to fibril conversion are yet poorly understood, thereby precluding the rational formulation of strategies aimed at targeting oligomeric species. In this review, we delve into the recent advances in the structural and mechanistic characterization of αS oligomers. We also discuss how these advances are transforming our understanding of these elusive species and paving the way for oligomer-targeting therapeutics and diagnosis.

中文翻译：

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α-突触核蛋白寡聚物的结构特性一瞥

α-突触核蛋白 (αS) 聚集是一组使人衰弱的神经退行性疾病的主要神经学标志，统称为突触核蛋白病，其中帕金森病最为常见。在聚集的初始阶段形成的αS寡聚体被认为是疾病发作和进展的关键致病驱动因素，是治疗干预和诊断的优先目标。然而，αS寡聚体的结构和寡聚体向原纤维转化的机制基础仍知之甚少，从而妨碍了针对寡聚体物种的合理制定策略。在这篇综述中，我们深入研究了 αS 低聚物结构和机械表征的最新进展。我们还讨论了这些进展如何改变我们对这些难以捉摸的物种的理解，并为寡聚物靶向治疗和诊断铺平道路。