Protein aggregation is the main hallmark of neurodegenerative diseases. Many proteins found in pathological inclusions are known to undergo liquid-liquid phase separation, a reversible process of molecular self-assembly. Emerging evidence supports the hypothesis that aberrant phase separation behavior may serve as a trigger of protein aggregation in neurodegeneration, and efforts to understand and control the underlying mechanisms are underway. Here, we review similarities and differences among four main proteins, α-synuclein, FUS, tau, and TDP-43, which are found aggregated in different diseases and were independently shown to phase separate. We discuss future directions in the field that will help shed light on the molecular mechanisms of aggregation and neurodegeneration.

蛋白质聚集是神经退行性疾病的主要标志。已知在病理性内含物中发现的许多蛋白质会经历液相-液相分离，这是分子自组装的可逆过程。越来越多的证据支持以下假设：相变异常行为可能是神经退行性病变中蛋白质聚集的触发因素，并且人们正在努力理解和控制潜在的机制。在这里，我们审查了四个主要蛋白质，α-突触核蛋白，FUS，tau和TDP-43之间的相似性和差异，这些蛋白在不同疾病中聚集在一起并独立显示出相分离。我们讨论该领域的未来方向，这将有助于阐明聚集和神经变性的分子机制。