Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias

Polyglutamine spinocerebellar ataxias (PolyQ SCAs) comprise a group of six inherited rare neurodegenerative diseases. They are caused by abnormal mutation of a CAG tract in six otherwise unrelated genes, leading to a complex cascade of molecular events that culminate in neuronal death. Based on decades of research in these diseases, this review identifies and categorizes the distinctive hallmarks involved in the molecular pathogenesis of PolyQ SCAs. We organized these molecular signatures into three groups: (i) primary hallmarks, which directly refer to the transcription and translation of the abnormally expanded gene and protein, respectively; (ii) secondary hallmarks, which include alterations in pathways and organelles that are implicated in the disease pathogenesis; and iii) end-stage hallmarks, which highlight the final events of the pathogenesis cascade in PolyQ SCAs. This framework is expected to provide a platform for understanding the complex network of molecular mechanisms involved in these diseases and to guide current and future efforts in developing therapies.

URI

http://hdl.handle.net/10400.1/27933

Editora

Springer Nature

DOI

10.1038/s41419-025-08154-2

Coleções

ABC2-Artigos (em revistas ou actas indexadas)
FCB2-Artigos (em revistas ou actas indexadas)

Licença CC

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