Neuronal PARIS-STAT3 axis drives tau pathology and glial activation in Alzheimers disease
Song, J.-Y.; Akkentili, F.; Jo, H.; Park, J.; Ha, S.; Redding_Ochoa, J.; Troncoso, J.; Kang, S.-U.; Dawson, V. L.; Dawson, T.
Show abstract
PARIS, a substrate of Parkin, accumulates in Parkinsons disease and promotes disease progression. Here, we demonstrate that PARIS also contributes to Alzheimers disease by elevating STAT3 transcriptional activity, thereby inducing tau pathology, hippocampal atrophy, and glial activation. Genetic depletion of Paris reduced tau phosphorylation and cognitive decline in tauopathy mice, whereas neuron-specific PARIS overexpression caused tau accumulation, gliosis, and memory impairment. In contrast, astrocyte-specific overexpression did not induce pathology, indicating that PARIS acts in neurons to drive tau phosphorylation and glial activation. The pathological features induced by neuronal PARIS overexpression were rescued by STAT3 inhibition, demonstrating that PARIS-STAT3 signaling underlies these effects. Moreover, Paris knockout did not alter pathology in the amyloid-driven mouse model, highlighting specificity for tau pathology. Together, these findings reveal PARIS as a neuronal regulator of STAT3 signaling that exacerbates tau-mediated neurodegeneration and identify the PARIS-STAT3 pathway as a potential therapeutic target in Alzheimers disease.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission 97%
- Entorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology 97%
- Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy 97%
Similar papers in this journal
Similar papers in this journal
- Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease 96%
- Tau assemblies enter the cytosol in a cholesterol sensitive process essential to seeded aggregation 96%
- Single cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging and disease 96%
Similar papers in this journal
"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.