Findings identify circTau6/cTau4R as a post-transcriptional mechanism that modulates tauopathy and partially recapitulated molecular signatures observed in human tauopathic brains.
It is reported that X-linked Dystonia-Parkinsonism (XDP), caused by a non-coding retrotransposon-associated repeat insertion in TAF1, involves a significant imbalance of tau isoforms and the accumulation of hyperphosphorylated, four-repeat tau in the brain.
C. J. Reyes, Aloysius Domingo, E. Penney et al.· medRxiv· 0 citations
Treatment with splicing modulator compounds that promote MAPT exon 10 exclusion reduced 4R tau expression and decreased the accumulation of hyperphosphorylated tau (pTau) and oligomeric and insoluble tau proteoforms, thereby rescuing tau-associated neuronal toxicity.
M. Silva, Hannah Lindmeier, Paolo Pigini et al.· Science Translational Medici...· 1 citation· ⚡1
Alternative splicing is a fundamental mechanism underlying protein diversity. The microtubule-associated protein tau (MAPT) undergoes age-associated alternative splicing of exon 10 to generate 3 R and 4 R isoforms, and disruption of the 4 R:3 R ratio is a central feature of tauopathies. However, the molecular mechanism...
BackgroundAbnormal tau hyperphosphorylation is a central feature of Alzheimer's disease (AD). Tau tubulin kinase 1 (TTBK1) is a key kinase involved in tau phosphorylation, but its upstream regulatory mechanisms remain poorly understood.ObjectiveTo identify circRNAs involved in the upstream regulation of TTBK1 and eluci...
Qing-Qing Li, Jie Xiao, Guo-Rong Deng et al.· Journal of Alzheimer's Disea...· 0 citations
Tauopathies encompass a heterogeneous group of neurodegenerative disorders characterized by the transition of tau from a microtubule-stabilizing protein into pathogenic, seed-competent species. Increasing evidence has redefined tau from a descriptive pathological hallmark to a pharmacologically actionable target across...
Tau assemblies, associated with tauopathies, are believed to self-propagate through prion-like mechanisms in the central nervous system, driving neurodegeneration. Recently, protein seed amplification assays have emerged as highly sensitive methods for detecting trace amounts of misfolded protein assemblies across vari...
Florian Almela, M. Bélondrade, R. Caillierez et al.· Acta Neuropathologica Commun...· 0 citations
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