Liquid–Liquid Phase Separation in Disease
- 3 December 2019
- journal article
- review article
- Published by Annual Reviews in Annual Review of Genetics
- Vol. 53 (1), 171-194
- https://doi.org/10.1146/annurev-genet-112618-043527
Abstract
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. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.Keywords
This publication has 152 references indexed in Scilit:
- The Central Dogma Decentralized: New Perspectives on RNA Function and Local Translation in NeuronsNeuron, 2013
- Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALSNeuron, 2011
- A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTDNeuron, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear importThe EMBO Journal, 2010
- Cell Signaling by Receptor Tyrosine KinasesCell, 2010
- The landscape of somatic copy-number alteration across human cancersNature, 2010
- Eukaryotic Stress Granules: The Ins and Outs of TranslationMolecular Cell, 2009
- A Systematic Survey Identifies Prions and Illuminates Sequence Features of Prionogenic ProteinsCell, 2009
- Phosphorylated TDP‐43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosisAnnals of Neurology, 2008