Abstract
Traumatic brain injury (TBI) is one of the important risk factors for the development of Alzheimer’s disease (AD). However, the molecular mechanism by which TBI promotes the progression of AD is not elucidated. In this study, we showed that the abnormal production of E2F1 is a major factor in promoting the neuropathological and cognitive deterioration of AD post-TBI. We found that repeated mild TBI can aggravate the neuropathology of AD in APP/PS1 mice. At the same time, the co-expression of E2F1 and beta-site APP cleaving enzyme 1 (BACE1) was upregulated when the mouse hippocampus was dissected. BACE1 is recognized as a rate-limiting enzyme for the production of Aβ. Here, we speculate that E2F1 may play a role in promoting BACE1 expression in AD. Therefore, we collected peripheral blood from patients with AD. Interestingly, there is a positive correlation between E2F1 and brain-derived neurotrophic factor–antisense (BDNF-AS), whereas BDNF-AS in AD can promote the expression of BACE1 and exhibit a neurotoxic effect. We established a cell model and found a regulatory relationship between E2F1 and BDNF-AS. Therefore, based on our results, we concluded that E2F1 regulates BDNF-AS, promotes the expression of BACE1, and affects the progression of AD. Furthermore, E2F1 mediates the TBI-induced neurotoxicity of AD.
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Abbreviations
- BDNF-AS:
-
Brain-derived nutritional factor antisense RNA
- TBI:
-
Traumatic brain injury
- BACE1:
-
Beta-site APP cleaving enzyme 1
- RA:
-
Retinoic acid
- LncRNA:
-
Long non-coding RNA
- NIA-AA:
-
National Institute on Aging–Alzheimer’s Association
- shRNA:
-
Short hairpin RNA
- siRNA:
-
Small interfering RNA
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This work was supported by the National Natural Science Foundation of China (82171296); the Joint Open Project of Jiangsu Key Laboratory for Tumor Biotherapy (XZSYSKF2020006); Science and Technology project of Changshu Health Commission (csws202010); Science and Technology project of Changshu No. 2 People’s Hospital (CSEY2021010); and Science and Technology project of “ke jiao xing wei” in Suzhou city (KJXW2021068). Basic and clinical transformation of non-coding RNA in Jiangsu Province Key laboratory open subject (202266).
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YJC and YTD designed the experiments. YTD, WKL, and ZW carried out the experiments. YJC and YTD provided the technical support. YJC, YTD, WKL, and ZW analyzed and compiled the data. YTD and WKL prepared the manuscript. The author(s) read and approved the final manuscript.
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Ding, Y., Luan, W., Shen, X. et al. E2F1 Mediates Traumatic Brain Injury and Regulates BDNF-AS to Promote the Progression of Alzheimer’s Disease. Neurotox Res 42, 17 (2024). https://doi.org/10.1007/s12640-024-00695-2
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DOI: https://doi.org/10.1007/s12640-024-00695-2