Novel treatments are desperately needed for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In this review article, a survey of emerging small-molecule approaches for ALS and FTD therapies is provided. These approaches include targeting aberrant liquid-liquid phase separation and stress granule assembly, modulation of RNA-protein interactions, inhibition of TDP-43 phosphorylation, inhibition of poly(ADP-ribose) polymerases (PARP), RNA-targeting approaches to reduce RAN translation of dipeptide repeat proteins from repeat expansions of C9ORF72, and novel autophagy activation pathways. This review details the emerging small-molecule tools and leads in these areas, along with a critical perspective on the key challenges facing these opportunities.

中文翻译：

---

新兴的小分子治疗方法，用于肌萎缩性侧索硬化症和额颞痴呆。

肌萎缩性侧索硬化症（ALS）和额颞痴呆（FTD）迫切需要新的治疗方法。在这篇评论文章中，提供了对ALS和FTD治疗的新兴小分子方法的调查。这些方法包括针对异常的液相-液相分离和应力颗粒组装，RNA-蛋白质相互作用的调节，TDP-43磷酸化的抑制，聚（ADP-核糖）聚合酶（PARP）的抑制，针对RNA的减少RAN翻译的方法C9ORF72的重复扩增产生的二肽重复蛋白，以及新颖的自噬激活途径。这篇综述详细介绍了新兴的小分子工具和在这些领域的领先地位，以及对这些机遇所面临的主要挑战的批判性观点。