Tunable tau expression in C. elegans neurons reveals that early-AD tau phosphorylation selectively impacts behavior and mitochondrial quality control - PubMed
6 hours ago
- #Alzheimer's disease
- #Tau phosphorylation
- #Mitochondrial quality control
- Tunable tau expression in C. elegans neurons was used to study the impact of early-AD tau phosphorylation, specifically at threonine 231 (T231).
- A series of 'tunable tau' strains were developed to compare the effects of tau pseudo-phosphorylation (T231E) and protein expression levels on phenotypic severity.
- T231E selectively influenced locomotory activity severity, which correlated with age and tau expression levels, but did not affect associative memory deficits.
- Mitophagy modulation was found to suppress T231E phenotypes, indicating a role for mitochondrial quality control in tau toxicity.
- A robust mitochondrial unfolded protein response (UPRmt) was observed in T231E strains, and loss of atfs-1, a key UPRmt transcription factor, suppressed T231E toxicity.
- The study suggests that enhancing mitophagy or managing UPRmt induction could be beneficial in addressing tau-related toxicity in Alzheimer's disease.