There is an increasing amount of evidence that biomolecular condensates are linked to neurodegenerative diseases associated with protein aggregation, such as Alzheimer’s disease and amyotrophic lateral sclerosis, although the mechanisms underlying this link remain elusive. In this Review, we summarize the possible connections between condensates and protein aggregation. We consider both liquid-to-solid transitions of phase-separated proteins and the partitioning of proteins into host condensates. We distinguish five key factors by which the physical and chemical environment of a condensate can influence protein aggregation, and we discuss their relevance in studies of protein aggregation in the presence of biomolecular condensates: increasing the local concentration of proteins, providing a distinct chemical microenvironment, introducing an interface wherein proteins can localize, changing the energy landscape of aggregation pathways, and the presence of chaperones in condensates. Analysing the role of biomolecular condensates in protein aggregation may be essential for a full understanding of amyloid formation and offers a new perspective that can help in developing new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.

越来越多的证据表明，生物分子凝聚物与蛋白质聚集相关的神经退行性疾病有关，例如阿尔茨海默病和肌萎缩侧索硬化症，尽管这种联系背后的机制仍然难以捉摸。在这篇综述中，我们总结了冷凝物和蛋白质聚集之间可能的联系。我们考虑相分离蛋白质的液固转变和蛋白质分配到宿主凝聚物中。我们区分了冷凝物的物理和化学环境影响蛋白质聚集的五个关键因素，并讨论了它们在生物分子冷凝物存在下的蛋白质聚集研究中的相关性：增加蛋白质的局部浓度，提供独特的化学微环境，引入蛋白质可以定位的界面，改变聚集途径的能量景观，以及凝聚物中分子伴侣的存在。分析生物分子缩合物在蛋白质聚集中的作用对于全面了解淀粉样蛋白的形成可能至关重要，并提供了一个新的视角，有助于开发预防和治疗神经退行性疾病的新治疗策略。