Eleanor and Lou Gehrig MDA/ALS Research Center, Neurological Institute, Columbia University Medical Center, 710 West 168th Street, New York, NY 10032, USA.
Curr Neurol Neurosci Rep. 2011 Feb;11(1):67-77. doi: 10.1007/s11910-010-0160-0.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of upper and lower motor neurons that causes progressive weakness and death. The breadth of research in ALS continues to grow with exciting new discoveries in disease pathogenesis and potential future therapeutics. There is a growing list of identified mutations in familial ALS, including those in genes encoding TDP-43 and FUS/TLS, which are expanding our understanding of the role of RNA modulation in ALS pathogenesis. There is a greater appreciation for the role of glial cells in motor neuron disease. Mitochondrial dysfunction is also being shown to be critical for motor neuron degeneration. In addition to pharmacotherapy, there are promising early developments with therapeutic implications in the areas of RNA interference, stem cell therapies, viral vector-mediated gene therapy, and immunotherapy. With greater understanding of ALS pathogenesis and exciting new therapeutic technologies, there is hope for future progress in treating this disease.
肌萎缩侧索硬化症(ALS)是一种影响上下运动神经元的神经退行性疾病,可导致进行性肌肉无力和死亡。ALS 研究领域不断拓展,疾病发病机制和潜在未来治疗方法方面不断有令人兴奋的新发现。家族性 ALS 中有越来越多的已识别突变,包括编码 TDP-43 和 FUS/TLS 的基因中的突变,这扩大了我们对 RNA 调节在 ALS 发病机制中的作用的理解。胶质细胞在运动神经元疾病中的作用也越来越受到重视。线粒体功能障碍也被证明对运动神经元退化至关重要。除了药物治疗外,在 RNA 干扰、干细胞疗法、病毒载体介导的基因治疗和免疫疗法等领域也有有前景的早期发展,具有治疗意义。随着对 ALS 发病机制的更深入了解和令人兴奋的新治疗技术的出现,有望在治疗这种疾病方面取得未来的进展。