San Gil Rebecca, Walker Adam K
Neurodegeneration Pathobiology Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Bioessays. 2025 Apr;47(4):e202400257. doi: 10.1002/bies.202400257. Epub 2025 Feb 3.
Neurons degenerate in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), causing progressive and inevitably fatal neurological decline. The best therapeutic strategies target underlying disease mediators, but after decades of intensive research, the causes of these neurodegenerative diseases remain elusive. Recently, coordinated activities of large consortia, increasing open access to large datasets, new methods such as cryo-transmission electron microscopy, and advancements in high-resolution omics technologies have offered new insights into the biology of disease that bring us closer to understanding mechanisms of neurodegeneration. In particular, improved understanding of the roles of the key pathological protein TAR DNA binding protein 43 (TDP-43) in disease has revealed intriguing new opportunities that provide hope for better diagnostic tools and effective treatments for ALS and FTD.
在肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）中，神经元会发生退化，导致进行性且不可避免的致命性神经功能衰退。最佳治疗策略针对潜在的疾病介质，但经过数十年的深入研究，这些神经退行性疾病的病因仍然不明。最近，大型研究联盟的协同活动、对大型数据集的开放获取增加、诸如冷冻透射电子显微镜等新方法以及高分辨率组学技术的进步，为疾病生物学提供了新的见解，使我们更接近了解神经退行性变的机制。特别是，对关键病理蛋白TAR DNA结合蛋白43（TDP - 43）在疾病中的作用有了更好的理解，揭示了有趣的新机会，为ALS和FTD提供更好的诊断工具和有效治疗带来了希望。
