MiR-409-5p as a Regulator of Neurite Growth Is Down Regulated in APP/PS1 Murine Model of Alzheimer’s Disease

Frontiers in Neuroscience

Bo Yu¹  Jun Wan²  Yifei Cai³  Yuan Wang³  Xiaoyang Ye³  Nana Ma³  Jing Guo³ 

[1] Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, China;Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China;Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University – The Hong Kong University of Science and Technology Medical Center, Shenzhen, China;Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University – The Hong Kong University of Science and Technology Medical Center, Shenzhen, China;

关键词: Alzheimer’s disease;    beta amyloid peptide;    microRNA;    mir-409-5p;    Plek;   

DOI  :  10.3389/fnins.2019.01264

来源: DOAJ

【 摘 要 】

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disease. Recent studies suggest that miRNA expression changes are associated with the development of AD. Our previous study showed that the expression level of miR-409-5p was stably downregulated in the early stage of APP/PS1 double transgenic mice model of AD. We now report that miR-409-5p impairs neurite outgrowth, decreases neuronal viability, and accelerates the progression of Aβ1–42-induced pathologies. In this study, we found that Aβ1–42 peptide significantly decreased the expression of miR-409-5p, which was consistent with the expression profile of miR-409-5p in the APP/PS1 mice cortexes. Plek was confirmed to be a potential regulatory target of miR-409-5p by luciferase assay and Western blotting. Overexpression of miR-409-5p has an obvious neurotoxicity in neuronal cell viability and differentiation, whereas Plek overexpression could partially rescue neurite outgrowth from this toxicity. Some cytoskeleton regulatory proteins have been found to be related to AD pathogenesis. Our data show some clues that cytoskeletal reorganization may play roles in AD pathology. The early downregulation of miR-409-5p in AD progression might be a self-protective reaction to alleviate the synaptic damage induced by Aβ, which may be used as a potential early biomarker of AD.

【 授权许可】

Unknown