Department of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USA.
Int J Mol Sci. 2018 Jun 9;19(6):1714. doi: 10.3390/ijms19061714.
Frontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in locus (), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-III), is associated with a rare hereditary subtype of FTD linked to chromosome 3 (FTD-3). ESCRT is involved in critical cellular processes such as multivesicular body (MVB) formation during endosomal⁻lysosomal pathway and autophagy. ESCRT mutants causes diverse physiological defects primarily due to accumulation of endosomes and defective MVBs resulting in misregulation of signaling pathways. Charged multivesicular body protein 2B (CHMP2B) is important for neuronal physiology which especially rely on precise regulation of protein homeostasis due to their post-mitotic status. has proven to be an excellent model for charaterization of mechanistic underpinning of neurodegenerative disorders including FTD. In this review, current understanding of various FTD-related mutations is discussed with a focus on models of CHMP2B-associated FTD.
额颞叶痴呆（FTD）是第二常见的老年神经退行性疾病。FTD 是一种异质性疾病，可以分为几个亚型。在 （）基因位点的突变，该基因编码内体分选复合物必需的运输 III（ESCRT-III）的一个组成部分，与与染色体 3（FTD-3）相关的罕见遗传性 FTD 亚型有关。ESCRT 参与关键的细胞过程，如内体-溶酶体途径和自噬过程中的多泡体（MVB）形成。ESCRT 突变体主要由于内体的积累和 MVB 的缺陷导致信号通路的失调，从而导致多种生理缺陷。带电多泡体蛋白 2B（CHMP2B）对神经元的生理学很重要，由于其有丝分裂后的状态，因此对蛋白质平衡的精确调节特别依赖。已被证明是研究包括 FTD 在内的神经退行性疾病发病机制的一个很好的模型。在这篇综述中，讨论了各种与 FTD 相关的突变的当前理解，并重点介绍了 CHMP2B 相关 FTD 的 模型。
