Osteoblast-Derived Lipocalin-2 Regulated by miRNA-96-5p/Foxo1 Advances the Progression of Alzheimer’s Disease

Abstract

Aim: Alzheimer’s disease (AD) is the most frequent cause of dementia and characterized by the accumulation of β-amyloid peptides in plaques and vessel walls. This study proposed a hypothesis of an inhibitory role of miR-96-5p in AD via regulating Foxo1. Methods & methods: AD mouse models were established by injecting with 1% pentobarbital. Results: Knockdown of miR-96-5p in the presence of naringin was shown to reduce the expression of Foxo1 and contents of superoxide dismutase, catalase and glutathione peroxidase, yet increase lipocalin-2 expression as well as hydroxyproline and malondialdehyde contents. Also, Foxo1-mediated lipocalin-2 inhibition attenuated AD. Conclusion: Our study shows downregulating miR-96-5p limited AD progression, highlighting miR-96-5p a potential therapeutic target in treating AD.

Keywords::

• Alzheimer’s disease
• Foxo1
• Lcn2
• miRNA-96-5p
• naringin
• osteoblasts

Acknowledgments

The authors acknowledge the reviewers for their helpful comments on this study.

Financial & competing interests disclosure

The present study was supported by Key Scientific and Technological Research Projects of Colleges and Universities in Hebei Province (ZD2019129), and Open Project Fund of Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, and Popular Science of Culture of Traditional Chinese Medicine Talents in Hebei Province in 2018 – Research and Research Ability Construction of Traditional Chinese Medicine Resources and Research on Classical Chinese Medicine Documents and Inheritance Schools (21810027), School Level Key Discipline Construction Project of Hebei University of Traditional Chinese Medicine (the 2nd batch in 2019), Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Master’s Degree Innovation Funding Project of Hebei Province (CXZZSS2020075), Key R&D Plan of Provincial Science and Technology Plan of Science and Technology Department of Hebei Province in 2019 – Biomedical Project (19277720D), Key Projects to Improve the Scientific and Technological Ability of Hebei University of Traditional Chinese Medicine in 2019 (KTZ2019017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

The present study was supported by Key Scientific and Technological Research Projects of Colleges and Universities in Hebei Province (ZD2019129), and Open Project Fund of Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, and Popular Science of Culture of Traditional Chinese Medicine Talents in Hebei Province in 2018 – Research and Research Ability Construction of Traditional Chinese Medicine Resources and Research on Classical Chinese Medicine Documents and Inheritance Schools (21810027), School Level Key Discipline Construction Project of Hebei University of Traditional Chinese Medicine (the 2nd batch in 2019), Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Master’s Degree Innovation Funding Project of Hebei Province (CXZZSS2020075), Key R&D Plan of Provincial Science and Technology Plan of Science and Technology Department of Hebei Province in 2019 – Biomedical Project (19277720D), Key Projects to Improve the Scientific and Technological Ability of Hebei University of Traditional Chinese Medicine in 2019 (KTZ2019017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.