AI Article Synopsis
- Friedreich ataxia (FRDA) is a genetic neurodegenerative disorder linked to mutations in the FXN gene, leading to mitochondrial issues and oxidative stress, with recent findings suggesting that shorter telomeres in patient lymphocytes may serve as a disease biomarker.
- Research confirmed telomere shortening in both leukocytes and cerebellar tissues from FRDA patients, while FRDA fibroblasts exhibited unexpectedly longer telomeres at early passages, driven by an alternative lengthening mechanism rather than telomerase activity.
- The study identified dysfunctional telomeres in FRDA cells, providing deeper insight into the disease's molecular mechanisms, which could inform future therapeutic strategies.
Article Abstract
Background: Friedreich ataxia (FRDA) is a progressive inherited neurodegenerative disorder caused by mutation of the FXN gene, resulting in decreased frataxin expression, mitochondrial dysfunction and oxidative stress. A recent study has identified shorter telomeres in FRDA patient leukocytes as a possible disease biomarker.
Results: Here we aimed to investigate both telomere structure and function in FRDA cells. Our results confirmed telomere shortening in FRDA patient leukocytes and identified similar telomere shortening in FRDA patient autopsy cerebellar tissues. However, FRDA fibroblasts showed significantly longer telomeres at early passage, occurring in the absence of telomerase activity, but with activation of an alternative lengthening of telomeres (ALT)-like mechanism. These cells also showed accelerated telomere shortening as population doubling increases. Furthermore, telomere dysfunction-induced foci (TIF) analysis revealed that FRDA fibroblasts have dysfunctional telomeres.
Conclusions: Our finding of dysfunctional telomeres in FRDA cells provides further insight into FRDA molecular disease mechanisms, which may have implications for future FRDA therapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462004 | PMC |
| http://dx.doi.org/10.1186/s13024-015-0019-6 | DOI Listing |
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