Upregulating ANKHD1 in PS19 mice reduces Tau phosphorylation and mitigates Tau-toxicity-induced cognitive deficits
Tian, X.; Le, N.; Zhao, Y.; Alawamleh, D. R.; Schwartz, A.; Meyer, L. E.; Helm, E. R.; Wu, C.
Show abstract
Abnormal accumulation of Tau protein in the brain disrupts normal cellular function and leads to neuronal death linked with many neurodegenerative disorders such as Alzheimers disease. An attractive approach to mitigate Tau-induced neurodegeneration is to enhance the clearance of toxic Tau aggregates. We previously showed that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration in fly disease models. Here we have generated a transgenic mouse line carrying Cre-inducible ANKHD1, the mouse homolog of mask, to determine whether the protective role of mask is conserved from flies to mammals. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we observed that ANKHD1 significantly reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, there was a notable trend towards reduced gliosis levels in these mice, suggesting a protective role of ANKHD1 against TauP301S-linked degeneration. Further analysis of 9-month- old mice revealed a similar trend of effects. Moreover, we found that ANKHD1 also suppresses the cognitive defect of 9-month-old PS19 female mice in novel object recognition (NOR) behavioral assay. Unlike previous therapeutic strategies that primarily focus on inhibiting Tau phosphorylation or directly clearing aggregates, this study highlights the novel role of ANKHD1 in promoting autophagy as a means to mitigate Tau pathology. This novel mechanism not only underscores ANKHD1s potential as a unique therapeutic target for tauopathies but also provides new insights into autophagy-based interventions for neurodegenerative diseases.
Matching journals
The top 13 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Diabetic phenotype in mouse and humans with β-amyloid pathology reduces the number of microglia around β-amyloid plaques 96%
- Amyloid plaque deposition accelerates tau propagation via activation of microglia in a humanized APP mouse model 94%
- A Trem2*R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques 94%
Similar papers in this journal
- Behavioral dysregulation and monoaminergic deficits precede memory impairments in human tau-overexpressing (htau) mice 96%
- Tau-tubulin kinase 1 and amyloid-β peptide induce phosphorylation of collapsin response mediator protein-2 and enhance neurite degeneration in Alzheimer disease mouse models 95%
- Protein farnesylation is upregulated in Alzheimer's human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer's model mice 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.