Abstract
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.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia in the elderly
We investigate the role of miR-409-5p in neurite outgrowth regulation by targeting Plek, which may contribute to the synaptic failure and cognitive dysfunction in AD
We found that the level of miR-4095p was stably downregulated from the early stage in APP/PS1 mice, which is consistent with the previous miRNA expression results of amyloid β (Aβ)-treated primary hippocampal neurons (Schonrock et al, 2010)
Summary
Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. It is an irreversible neurodegenerative disorder, with the hallmarks of senile plaques, neurofibrillary tangles (NFTs), and neuronal loss (Barker et al, 2002; Vinters, 2015). MiR-409-5p-Regulated Neurite Outgrowth in AD Pathologies (Robakis, 2011). It has been widely explored, the exact pathogenesis of AD remains to be elucidated. MiRs have the ability to regulate cytoskeletal changes in many diseases especially cancers (Gross, 2013; Kanakkanthara and Miller, 2013; Zhang et al, 2019) Cytoskeletal abnormalities and synaptic impairment are typical in amyloid β (Aβ)-induced stress (Bamburg and Bernstein, 2016). miRs have the ability to regulate cytoskeletal changes in many diseases especially cancers (Gross, 2013; Kanakkanthara and Miller, 2013; Zhang et al, 2019)
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