PDF(Pubmed)
Abstract：
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with severe socio-economic impact. A hallmark of ALS pathology is the presence of aberrant cytoplasmic inclusions composed of misfolded and aggregated proteins, including both wild-type and mutant forms. This review highlights the critical role of misfolded protein species in ALS pathogenesis, particularly focusing on Cu/Zn superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP-43), and emphasizes the urgent need for innovative therapeutic strategies targeting these misfolded proteins directly. Despite significant advancements in understanding ALS mechanisms, the disease remains incurable, with current treatments offering limited clinical benefits. Through a comprehensive analysis, the review focuses on the direct modulation of the misfolded proteins and presents recent discoveries in small molecules and peptides that inhibit SOD1 and TDP-43 aggregation, underscoring their potential as effective treatments to modify disease progression and improve clinical outcomes.
摘要：
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，具有严重的社会经济影响。ALS病理学的一个标志是存在由错误折叠和聚集的蛋白质组成的异常细胞质内含物。包括野生型和突变体形式。这篇综述强调了错误折叠蛋白在ALS发病机理中的关键作用。特别关注铜/锌超氧化物歧化酶（SOD1）和TARDNA结合蛋白43（TDP-43），并强调迫切需要直接针对这些错误折叠蛋白的创新治疗策略。尽管在理解ALS机制方面取得了重大进展，这种疾病仍然无法治愈，目前的治疗提供有限的临床益处。通过综合分析,该综述侧重于错误折叠蛋白的直接调节，并介绍了抑制SOD1和TDP-43聚集的小分子和肽的最新发现，强调它们作为有效治疗方法的潜力，以改变疾病进展和改善临床结果。
