Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, College of Life Sciences, Sichuan University, Chengdu, China.
Small GTPases. 2022 Jan;13(1):56-76. doi: 10.1080/21541248.2021.1892443. Epub 2021 Mar 5.
The hexanucleotide repeat (GGGGCC) expansion in is accounted for a large proportion of the genetic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The hypotheses of how the massive G4C2 repeats in destroy the neurons and lead to ALS/FTD are raised and improving. As a multirole player, C9orf72 exerts critical roles in many cellular processes, including autophagy, membrane trafficking, immune response, and so on. Notably, the partners of C9orf72, through which C9orf72 participates in the cell activities, have been identified. Notably, the structures of the C9orf72-SMCR8-WDR41 complex shed light on its activity as GTPase activating proteins (GAP). In this manuscript, we reviewed the latest research progress in the C9orf72-mediated ALS/FTD, the physiological functions of C9orf72, and the putative function models of C9orf72/C9orf72-containing complex.
在 中发现的六核苷酸重复（GGGGCC）扩张占很大比例的遗传肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）。大量 G4C2 重复序列如何破坏神经元并导致 ALS/FTD 的假说不断被提出和完善。作为一个多角色扮演者，C9orf72 在许多细胞过程中发挥关键作用，包括自噬、膜运输、免疫反应等。值得注意的是，C9orf72 的伴侣已经被确定，通过这些伴侣，C9orf72 参与细胞活动。值得注意的是，C9orf72-SMCR8-WDR41 复合物的结构阐明了其作为 GTP 酶激活蛋白（GAP）的活性。在本文中，我们综述了 C9orf72 介导的 ALS/FTD 的最新研究进展、C9orf72 的生理功能以及 C9orf72/包含 C9orf72 复合物的假设功能模型。
