the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Neurobiol Dis. 2022 Aug;170:105749. doi: 10.1016/j.nbd.2022.105749. Epub 2022 May 11.
Increasing genetic and biochemical evidence has broadened our view of the pathomechanisms that lead to Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases with similar symptoms and causes. Stress granules are dynamic cytosolic storage hubs for mRNAs in response to stress exposures, that are evolutionarily conserved cytoplasmic RNA granules in somatic cells. A lot of previous studies have shown that the impaired stress granules are crucial events in SMA/ALS pathogenesis. In this review, we described the key stress granules related RNA binding proteins (SMN, TDP-43, and FUS) involved in SMA/ALS, summarized the reported mutations in these RNA binding proteins involved in SMA/ALS pathogenesis, and discussed the mechanisms through which stress granules dynamics participate in the diseases. Meanwhile, we described the applications and limitation of current therapies targeting SMA/ALS. We futher proposed the promising targets on stress granules in the future therapeutic interventions of SMA/ALS.
越来越多的遗传和生化证据拓宽了我们对导致脊髓性肌萎缩症（SMA）和肌萎缩侧索硬化症（ALS）的病理机制的认识，这两种致命的神经退行性疾病具有相似的症状和病因。应激颗粒是细胞应对应激时，mRNA 的动态细胞溶质储存中心，是体细胞中进化保守的细胞质 RNA 颗粒。大量先前的研究表明，受损的应激颗粒是 SMA/ALS 发病机制中的关键事件。在这篇综述中，我们描述了与 SMA/ALS 相关的关键应激颗粒相关 RNA 结合蛋白（SMN、TDP-43 和 FUS），总结了这些 RNA 结合蛋白在 SMA/ALS 发病机制中的报道突变，并讨论了应激颗粒动力学参与疾病的机制。同时，我们描述了目前针对 SMA/ALS 的治疗方法的应用和局限性。我们进一步提出了在未来 SMA/ALS 的治疗干预中应激颗粒的有前途的靶点。
