Among the large variety of neurodegenerative disorders, polyglutamine (polyQ) diseases comprise a distinct group of rare autosomal-dominantly inherited health conditions, characterized by the expansion of a glutamine-coding CAG trinucleotide repeat within the causative genes. To date, nine different polyQ diseases have been described: dentatorubral-pallidoluysian atrophy (DRPLA), Huntington disease (HD), spinobulbar muscular atrophy (SBMA), as well as the spinocerebellar ataxias 1, 2, 3 (also known as Machado-Joseph disease, MJD), 6, 7, and 17. Although the disease proteins differ in structure and function, the expanded polyQ stretch can trigger comparable molecular consequences, eventually leading to neuronal demise and disease manifestation.
This Research Topic focuses on the commonalities of polyQ diseases in the context of posttranslational modifications (PTMs) and their relevance in the molecular pathogenesis. All polyQ disease proteins are targets of PTMs, which include acetylation, glycosylation, lipidation, phosphorylation, non-proteasomal proteolysis, SUMOylation, and ubiquitination. These molecular changes impact the disease protein function, localization, and stability, and can modulate their pathological aggregation-prone nature. Interestingly, the Machado-Joseph disease protein ataxin-3 itself is actively involved in PTMs, as it acts as a deubiquitinase that modifies polyubiquitin chains on substrate proteins. Comparative insights in disease-relevant PTMs may provide further details about the physiological roles of the respective native and disease proteins and facilitate the discovery of novel therapeutic targets for polyQ diseases.
We encourage expert scientists in the field to submit their original research, brief research reports, commentary, method-specific articles, opinion articles, and reviews on the role of PTMs in polyQ diseases. The resulting compilation of the latest findings and current knowledge will help us to deepen our understanding of the molecular pathology of these yet incurable disorders.
Among the large variety of neurodegenerative disorders, polyglutamine (polyQ) diseases comprise a distinct group of rare autosomal-dominantly inherited health conditions, characterized by the expansion of a glutamine-coding CAG trinucleotide repeat within the causative genes. To date, nine different polyQ diseases have been described: dentatorubral-pallidoluysian atrophy (DRPLA), Huntington disease (HD), spinobulbar muscular atrophy (SBMA), as well as the spinocerebellar ataxias 1, 2, 3 (also known as Machado-Joseph disease, MJD), 6, 7, and 17. Although the disease proteins differ in structure and function, the expanded polyQ stretch can trigger comparable molecular consequences, eventually leading to neuronal demise and disease manifestation.
This Research Topic focuses on the commonalities of polyQ diseases in the context of posttranslational modifications (PTMs) and their relevance in the molecular pathogenesis. All polyQ disease proteins are targets of PTMs, which include acetylation, glycosylation, lipidation, phosphorylation, non-proteasomal proteolysis, SUMOylation, and ubiquitination. These molecular changes impact the disease protein function, localization, and stability, and can modulate their pathological aggregation-prone nature. Interestingly, the Machado-Joseph disease protein ataxin-3 itself is actively involved in PTMs, as it acts as a deubiquitinase that modifies polyubiquitin chains on substrate proteins. Comparative insights in disease-relevant PTMs may provide further details about the physiological roles of the respective native and disease proteins and facilitate the discovery of novel therapeutic targets for polyQ diseases.
We encourage expert scientists in the field to submit their original research, brief research reports, commentary, method-specific articles, opinion articles, and reviews on the role of PTMs in polyQ diseases. The resulting compilation of the latest findings and current knowledge will help us to deepen our understanding of the molecular pathology of these yet incurable disorders.