Publications by authors named "Sarah Lyn Rea"
Article Synopsis
- Mutations in the TBK1 gene are linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), accounting for about 3-4% of cases with over 100 distinct mutations identified.
- Missense mutations' disease mechanisms remain unclear, but they may affect TBK1's role in neuroinflammation and autophagy regulation.
- The review summarizes the functional effects of TBK1 missense mutations and provides new modeling data predicting their structural impacts.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis and frontotemporal lobar degeneration are multifaceted diseases with genotypic, pathological and clinical overlap. One such overlap is the presence of SQSTM1/p62 mutations. While traditionally mutations manifesting in the ubiquitin-associated domain of p62 were associated with Paget's disease of bone, mutations affecting all functional domains of p62 have now been identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients.
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