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Identification of potential therapeutic and diagnostic characteristics of Alzheimer disease by targeting the miR-132-3p/FOXO3a-PPM1F axis in APP/PS1 mice

Fu, Xiaofeng, Liu, Jing, Xie, Junjie, Chen, Guanhong, Zhang, Hao, Meng, Fantao, Wu, Min, Li, Qiongyu, Liu, Yong, Wang, Wentao, Dai, Juanjuan, Wang, Dan, Zhao, Di, Li, Chen, Wang, Xuezhen·2022·Brain Research
DOI 10.1016/j.brainres.2022.147983
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Abstract

Alzheimer disease (AD) is a neurodegenerative disorder, which is characterized by progressive impairment of memory and cognition. Early diagnosis and treatment of AD has become a leading topic of research. In this study, we explored the effects of the miR-132-3p/FOXO3a-PPM1F axis on the onset of AD for possible early diagnosis and therapy. We found that miR-132-3p levels in the hippocampus and blood were drastically decreased in APP/PS1 mice from 9 months of age, and bi-directional manipulation of miR-132-3p levels induced magnified effects on learning memory behaviors, and manifestation of AD-related pathological characteristics and inflammatory cytokines in APP/PS1 mice of relevant ages. The hippocampal PPM1F expression levels were significantly elevated in APP/PS1 mice from 3 months of age, which was correlated with miR-132-3p levels at different ages. Overexpression of PPM1F remarkably accelerated the progression of learning memory deficits and associated pathological factors in APP/PS1 mice. Further, we showed that miR-132-3p modulated the expression of PPM1F via FOXO3a in HT22 cells. Finally, using peripheral blood samples of human study participants, we found that the miR-132-3p and PPM1F expression levels in patients with AD were also altered with prominent correlations. In conclusion, miR-132-3p indirectly regulates PPM1F expression by targeting FOXO3a, which could play an extensive role in contributing to the establishment of early diagnosis, treatment, and pathogen…

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Metadata

Authors
Fu, X., Liu, J., Xie, J., Chen, G., Zhang, H., Meng, F., Wu, M., Li, Q., Liu, Y., Wang, W., Dai, J., Wang, D., Zhao, D., Li, C., & Wang, X.
ORCID
Wang, Xuezhen
Venue
Brain Research
Publisher
Elsevier BV
Published
2022-09
Volume
1790
Pages
147983
ISSN
0006-8993
DOI
10.1016/j.brainres.2022.147983
Cited by
13
References
5
Language
en
Licence
Funders
  • National Natural Science Foundation of China (82171521)
  • Natural Science Foundation of Shandong Province (ZR2019PH109, ZR2021MH073, ZR2021MH206)
  • Binzhou Medical University (BY2020KJ02)

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