Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice
| Title: | Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice |
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| Authors: | Yanli Zhang, Tian Li, Jie Miao, Zhina Zhang, Mingxuan Yang, Zhuoran Wang, Bo Yang, Jiawei Zhang, Haiting Li, Qiang Su, Junhong Guo |
| Source: | Neural Regeneration Research, Vol 20, Iss 2, Pp 533-547 (2025) |
| Publisher Information: | Wolters Kluwer Medknow Publications, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Neurology. Diseases of the nervous system |
| Subject Terms: | alzheimer’s disease, amyloid-β, app/ps1 mice, cerebrovascular endothelial cells, cognitive deficits, gamma-glutamyl transferase 5, neurovascular unit, nuclear factor‐kappa b, synaptic plasticity, β-site app cleaving enzyme 1, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: | In patients with Alzheimer’s disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer’s disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease (Aβ1–42–treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-β in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of β-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1673-5374 1876-7958 |
| Relation: | https://journals.lww.com/10.4103/NRR.NRR-D-23-01525; https://doaj.org/toc/1673-5374; https://doaj.org/toc/1876-7958 |
| DOI: | 10.4103/NRR.NRR-D-23-01525 |
| Access URL: | https://doaj.org/article/d81ff55711794bcdb8272084820874d7 |
| Accession Number: | edsdoj.81ff55711794bcdb8272084820874d7 |
| Database: | Directory of Open Access Journals |
| ISSN: | 16735374 18767958 |
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| DOI: | 10.4103/NRR.NRR-D-23-01525 |
| Published in: | Neural Regeneration Research |
| Language: | English |