Publications by authors named "Rana D Incebacak Eltemur"
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia caused by a polyglutamine-coding CAG repeat expansion in the ATXN3 gene. While the CAG length correlates negatively with the age at onset, it accounts for approximately 50% of its variability only. Despite larger efforts in identifying contributing genetic factors, candidate genes with a robust and plausible impact on the molecular pathogenesis of MJD are scarce.
View Article and Find Full Text PDFLysine residues are one of the main sites for posttranslational modifications of proteins, and lysine ubiquitination of the Machado-Joseph disease protein ataxin-3 is implicated in its cellular function and polyglutamine expansion-dependent toxicity. Despite previously undertaken efforts, the individual roles of specific lysine residues of the ataxin-3 sequence are not entirely understood and demand further analysis. By retaining single lysine residues of otherwise lysine-free wild-type and polyglutamine-expanded ataxin-3, we assessed the effects of a site-limited modifiability on ataxin-3 protein levels, aggregation propensity, localization, and stability.
View Article and Find Full Text PDFArticle Synopsis
- Directed proteolytic processes significantly affect protein integrity, with calcium-activated calpains being key modulators due to their unique proteolytic activity.
- In neurodegenerative diseases, particularly polyglutamine disorders, calpains contribute to harmful breakdown products of disease proteins, linking them to the disease's molecular pathogenesis.
- This review emphasizes the importance of calpains in these disorders and encourages further research to explore calpain-mediated proteolysis as a potential therapeutic target in neurodegeneration.
Article Synopsis
- Machado-Joseph disease (MJD) is linked to the abnormal expansion of the polyglutamine tract in the ataxin-3 protein, leading to its accumulation in the nucleus and formation of aggregates in neurons.
- Research focuses on the nuclear transport receptor KPNB1, which interacts with both normal and polyQ-expanded ataxin-3, but doesn't change its location in cells.
- Modulating KPNB1 levels affects ataxin-3 levels and cell survival, suggesting KPNB1's role in regulating ataxin-3 turnover and pointing to it as a potential therapeutic target for MJD.
Article Synopsis
- Spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease linked to a genetic mutation in the TBP gene, leading to toxic protein fragments.
- Calcium-dependent calpain proteases play a critical role in the disease by cleaving TBP and causing protein depletion in neurons.
- Inhibiting calpain activity has been shown to reduce TBP cleavage and improve cell viability, highlighting their importance in SCA17's molecular pathogenesis.