Baz-Therapeutics Inc., 810 Rittenhouse Square, Suite 412, Philadelphia, PA 19103, USA.
Clinical Research Building, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Biomolecules. 2024 Oct 18;14(10):1324. doi: 10.3390/biom14101324.
Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.
蛋白构象病涉及特定蛋白质的异常积累。维持蛋白质组的平衡是一个由负责蛋白质合成、折叠和降解的细胞机制的复杂网络精细调控的过程。然而,压力和衰老会破坏这种平衡,导致广泛的蛋白质聚集。目前,有几种针对肌萎缩侧索硬化症的蛋白聚集的治疗方法正在临床试验中。这些方法主要集中在两种策略上:针对由于突变而容易聚集的蛋白质,以及针对维持蛋白质内稳性以防止聚集的细胞机制。本综述将涵盖这些新兴药物。肌萎缩侧索硬化症研究的进展不仅为肌萎缩侧索硬化症患者带来了更好的治疗效果的希望,还为神经退行性疾病药物发现的更广泛领域提供了有价值的见解和方法。