Frontotemporal dementia is a group of early onset dementia syndromes linked to underlying frontotemporal lobar degeneration (FTLD) pathology that can be classified based on the formation of abnormal protein aggregates involving tau and two RNA binding proteins, TDP-43 and FUS. Although elucidation of the mechanisms leading to FTLD pathology is in progress, recent advances in genetics and neuropathology indicate that a majority of FTLD cases with proteinopathy involving RNA binding proteins show highly congruent genotype-phenotype correlations. Specifically, recent studies have uncovered the unique properties of the low-complexity domains in RNA binding proteins that can facilitate liquid-liquid phase separation in the formation of membraneless organelles. Furthermore, there is compelling evidence that mutations in FTLD genes lead to dysfunction in diverse cellular pathways that converge on the endolysosomal pathway, autophagy, and neuroinflammation. Together, these results provide key mechanistic insights into the pathogenesis and potential therapeutic targets of FTLD.

中文翻译：

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RNA结合蛋白和额颞叶变性的发病机理。

额颞痴呆是一组与基础额颞叶变性（FTLD）病理相关的早期发作性痴呆综合征，可根据涉及tau和两种RNA结合蛋白TDP-43和FUS的异常蛋白聚集体的形成进行分类。尽管目前尚不清楚导致FTLD病理的机制，但遗传学和神经病理学的最新进展表明，大多数涉及RNA结合蛋白的蛋白病FTLD病例均表现出高度一致的基因型与表型相关性。具体而言，最近的研究发现了RNA结合蛋白中低复杂度结构域的独特特性，该特性可以促进无膜细胞器形成过程中的液相分离。此外，有令人信服的证据表明，FTLD基因的突变会导致多种细胞途径功能障碍，这些途径会集中在溶酶体途径，自噬和神经炎症上。总之，这些结果为FTLD的发病机理和潜在的治疗靶点提供了关键的力学见解。