Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK, CB2 0XY.
Tanz Centre for Research in Neurodegenerative Diseases, and Departments of Medicine, University of Toronto, Toronto, Ontario, Canada, M5S 3H2.
Hum Mol Genet. 2019 Nov 21;28(R2):R187-R196. doi: 10.1093/hmg/ddz162.
Recent work on the biophysics of proteins with low complexity, intrinsically disordered domains that have the capacity to form biological condensates has profoundly altered the concepts about the pathogenesis of inherited and sporadic neurodegenerative disorders associated with pathological accumulation of these proteins. In the present review, we use the FUS, TDP-43 and A11 proteins as examples to illustrate how missense mutations and aberrant post-translational modifications of these proteins cause amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD).
近期对具有低复杂度、内在无序结构域的蛋白质生物物理学的研究，这些结构域具有形成生物凝聚物的能力，极大地改变了与这些蛋白质病理性积累相关的遗传性和散发性神经退行性疾病发病机制的概念。在本综述中，我们使用 FUS、TDP-43 和 A11 蛋白作为示例，说明这些蛋白的错义突变和异常的翻译后修饰如何导致肌萎缩侧索硬化症（ALS）和额颞叶变性（FTLD）。
