Tenascin‐R aggravates Aβ production in the perforant pathway by regulating Nav1.6 activity in APP/PS1 mice
Nodes of Ranvier-associated tenascin-R (Tn-R) regulate amyloid beta (Aβ) production in the perforant pathway of APP/PS1 mice. Tn-R enhances Nav1.6-mediated sodium currents, promoting amyloid precursor protein (APP) transcription and Aβ generation. Genetic downregulation of Tn-R mitigates Aβ deposition, restores synaptic integrity, and improves cognition. The conserved GEDC motif within Tn-R's epidermal growth factor-like domain is critical for modulating Nav1.6 activity and amyloidogenesis. The Tn-R/Nav1.6 axis represents a novel therapeutic target for Alzheimer's disease, with GEDC-derived peptides offering translational potential.
Authors
- Lang‐Man Lv
- Zhi‐Cheng Xiao (ORCID: https://orcid.org/0000-0001-5172-762X)
- Qi‐Fa Li
- Jie Luo (ORCID: https://orcid.org/0009-0003-6832-0238)
- Yifan Zhao (ORCID: https://orcid.org/0000-0001-8986-9164)
- Shao Li (ORCID: https://orcid.org/0000-0002-4889-8636)
- Quanhong Ma (ORCID: https://orcid.org/0000-0001-9392-8956)
- Ai‐Ping Li
- Bin Wang (ORCID: https://orcid.org/0000-0002-8403-080X)
- Xi Wang (ORCID: https://orcid.org/0000-0002-7869-3041)
- Yue Kong
- Ziyan Wang (ORCID: https://orcid.org/0000-0003-2017-1993)
- Rong Jiang (ORCID: https://orcid.org/0009-0000-7642-932X)
- Xuewei Yang (ORCID: https://orcid.org/0000-0003-0380-9588)
- Jincheng Lu
- Guang Yang (ORCID: https://orcid.org/0000-0002-0012-3831)
Institutions
- Binzhou Medical University (CN)
- Shandong University of Aeronautics (CN)
- Dalian Medical University (CN)
- Yuhuangding Hospital (CN)
- Soochow University (CN)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
- Monash University (AU)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1002/alz.70633
- Citations
- 1
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Liaoning Province
- Natural Science Foundation of Shandong Province