期刊
SCIENCE
卷 370, 期 6512, 页码 56-60出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abb8032
关键词
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资金
- HHMI
- NIH [R35NS097974, 5R01NS056114]
- NSF [MCB1614766]
- St. Jude Children's Research Hospital Research Collaborative on Membraneless Organelles
Over the past decade, phase transitions have emerged as a fundamental mechanism of cellular organization. In parallel, a wealth of evidence has accrued indicating that aberrations in phase transitions are early events in the pathogenesis of several neurodegenerative diseases. We review the key evidence of defects at multiple levels, from phase transition of individual proteins to the dynamic behavior of complex, multicomponent condensates in neurodegeneration. We also highlight two concepts, dynamical arrest and heterotypic buffering, that are key to understanding how pathological phase transitions relate to pleiotropic defects in cellular functions and the accrual of proteinaceous deposits at end-stage disease. These insights not only illuminate disease etiology but also are likely to guide the development of therapeutic interventions to restore homeostasis.
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