Malik Ravinder, Wiedau Martina
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Front Mol Neurosci. 2020 Jun 9;13:98. doi: 10.3389/fnmol.2020.00098. eCollection 2020.
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease that targets motor neurons (MNs) in the brain and spinal cord. It leads to gradual loss of motor signals to muscles leading to atrophy and weakness. Most patients do not survive for more than 3-5 years after disease onset. Current ALS treatments provide only a small delay of disease progression. Therefore, it is of utmost importance to explore new therapeutic approaches. One of the major hindrances in achieving this goal is poor understanding of causes of the disease. ALS has complex pathophysiological mechanisms in its genetic and sporadic forms. Protein aggregates are a common hallmark of ALS regardless of cause making protein pathways attractive therapeutic targets in ALS. Here, we provide an overview of compounds in different stages of pharmacological development and their protein pathway targets.
肌萎缩侧索硬化症（ALS）是一种使人衰弱的神经退行性疾病，它靶向大脑和脊髓中的运动神经元（MNs）。它会导致传向肌肉的运动信号逐渐丧失，从而导致萎缩和无力。大多数患者在疾病发作后存活时间不超过3至5年。目前的ALS治疗方法只能略微延缓疾病进展。因此，探索新的治疗方法至关重要。实现这一目标的主要障碍之一是对该疾病病因的了解不足。ALS在其遗传型和散发型中具有复杂的病理生理机制。无论病因如何，蛋白质聚集体都是ALS的一个常见标志，这使得蛋白质途径成为ALS中具有吸引力的治疗靶点。在这里，我们概述了处于不同药理学开发阶段的化合物及其蛋白质途径靶点。
