Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Aimcan Pharma Research & Technologies, 398 Laird Rd, Guelph, ON N1G 3X7, Canada.
Drug Discov Today. 2015 Jan;20(1):65-75. doi: 10.1016/j.drudis.2014.08.016. Epub 2014 Sep 6.
Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weight loss and respiratory failure. Evidence suggests that inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are all responsible for ALS pathogenesis. We review neuroprotective agents with the ability to reduce ALS-related bodyweight loss, summarize the various therapies tested on animal models targeting the proposed molecular mechanisms, compare their effects on bodyweight loss, muscle damage, disease onset, duration and survival, and analyze their structure-activity relationships, with the overall goal of creating a screening strategy for further clinical application.
肌萎缩侧索硬化症（ALS）是一种使人虚弱的疾病，其特征是运动神经元逐渐丧失，导致肌肉萎缩、体重减轻和呼吸衰竭。有证据表明，炎症、氧化应激、线粒体功能障碍、细胞凋亡、谷氨酸兴奋性毒性和蛋白酶体功能障碍都与 ALS 的发病机制有关。我们综述了具有减轻 ALS 相关体重减轻作用的神经保护剂，总结了针对所提出的分子机制在动物模型中测试的各种治疗方法，比较了它们对体重减轻、肌肉损伤、疾病发作、持续时间和存活率的影响，并分析了它们的结构-活性关系，总体目标是创建一个筛选策略，以进一步临床应用。
