Back to Search Start Over

Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer’s disease

Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer’s disease

Authors :
Lan-Ting Zhou
Dan Liu
Hui-Cong Kang
Lu Lu
He-Zhou Huang
Wen-Qing Ai
Yang Zhou
Man-Fei Deng
Hao Li
Zhi-Qiang Liu
Wei-Feng Zhang
Ya-Zhuo Hu
Zhi-Tao Han
Hong-Hong Zhang
Jian-Jun Jia
Avijite Kumer Sarkar
Saldin Sharaydeh
Jie Wang
Heng-Ye Man
Marcel Schilling
Lars Bertram
Youming Lu
Ziyuan Guo
Ling-Qiang Zhu
Source :
Science Advances. 9
Publication Year :
2023
Publisher :
American Association for the Advancement of Science (AAAS), 2023.

Abstract

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 3×Tg 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.

Subjects

Subjects :
Multidisciplinary

Details

ISSN :
23752548
Volume :
9
Database :
OpenAIRE
Journal :
Science Advances
Accession number :
edsair.doi...........ac23785ce36d9410b06d65db463b3ad7
Full Text :
https://doi.org/10.1126/sciadv.abq7105