1421-Hallmarks of Polyglutamine Spinocerebellar Ataxias

The review article examines the pathogenesis of polyglutamine spinocerebellar ataxias (PolyQ SCAs), a group of six inherited neurodegenerative disorders caused by CAG repeat mutations. The authors establish a conceptual framework by categorizing the disease mechanisms into eleven molecular hallmarks divided into three distinct stages. Primary hallmarks involve direct consequences of the mutation, such as protein aggregation, aberrant molecular interactions, posttranslational modifications, and RNA-mediated toxicity. Secondary hallmarks describe resulting cellular dysfunctions, including mitochondrial impairment, degradation system failures, transcriptional dysregulation, and calcium signaling imbalances. Finally, end-stage hallmarks identify the culminating events of neuroinflammation and selective neuronal loss. This comprehensive overview serves as a platform for understanding the complex pathological network of PolyQ SCAs and aims to guide the development of future therapeutic strategies.References:Nóbrega C, Marcelo A, Rajado A T, et al. Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias[J]. Cell Death & Disease, 2025, 16(1): 826.前往小宇宙评论区与主播互动