Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, 01307 Dresden, Germany; email:
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Annu Rev Genet. 2019 Dec 3;53:171-194. doi: 10.1146/annurev-genet-112618-043527. Epub 2019 Aug 20.
We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ability to develop effective disease treatments. To overcome this limitation, we need new concepts to describe and comprehend the complex mechanisms underlying human diseases. Condensate formation by phase separation emerges as a new principle to explain the organization of living cells. In this review, we present emerging evidence that aberrant forms of condensates are associated with many human diseases, including cancer, neurodegeneration, and infectious diseases. We examine disease mechanisms driven by aberrant condensates, and we point out opportunities for therapeutic interventions. We conclude that phase separation provides a useful new framework to understand and fight some of the most severe human diseases.
近年来，我们在确定许多人类疾病的遗传原因方面取得了快速进展。然而，尽管取得了这一最近的进展，我们对这些疾病的机制理解往往并不完整。这是一个问题，因为它限制了我们开发有效疾病治疗方法的能力。为了克服这一限制，我们需要新的概念来描述和理解人类疾病的复杂机制。相分离形成凝聚物的现象作为一个新的原理出现，用以解释活细胞的组织。在这篇综述中，我们提出了新的证据，表明凝聚物的异常形式与许多人类疾病有关，包括癌症、神经退行性疾病和传染病。我们研究了由异常凝聚物驱动的疾病机制，并指出了治疗干预的机会。我们得出的结论是，相分离为理解和对抗一些最严重的人类疾病提供了一个有用的新框架。
