| First Author | Zhou LT | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 16 | Pages | eabq7105 |
| PubMed ID | 37083538 | Mgi Jnum | J:337545 |
| Mgi Id | MGI:7468236 | Doi | 10.1126/sciadv.abq7105 |
| Citation | Zhou LT, et al. (2023) Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease. Sci Adv 9(16):eabq7105 |
| abstractText | The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer's disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3xTg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD. |
