Apoptosis and Cell Death Research Program, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, United States.
Beilstein J Org Chem. 2013 Apr 15;9:717-32. doi: 10.3762/bjoc.9.82. Print 2013.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few therapeutic options. While several gene mutations have been implicated in ALS, the exact cause of neuronal dysfunction is unknown and motor neurons of affected individuals display numerous cellular abnormalities. Ongoing efforts to develop novel ALS treatments involve the identification of small molecules targeting specific mechanisms of neuronal pathology, including glutamate excitotoxicity, mutant protein aggregation, endoplasmic reticulum (ER) stress, loss of trophic factors, oxidative stress, or neuroinflammation. Herein, we review recent advances in the discovery and preclinical characterization of lead compounds that may ultimately provide novel drugs to treat patients suffering from ALS.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，治疗选择有限。虽然已经有几种基因突变与 ALS 有关，但神经元功能障碍的确切原因尚不清楚，而且受影响个体的运动神经元表现出许多细胞异常。目前正在努力开发新的 ALS 治疗方法，包括确定针对神经元病理学特定机制的小分子，这些机制包括谷氨酸兴奋性毒性、突变蛋白聚集、内质网（ER）应激、营养因子丧失、氧化应激或神经炎症。在此，我们综述了在发现和临床前鉴定先导化合物方面的最新进展，这些化合物最终可能为治疗 ALS 患者提供新的药物。
