microRNA-9 attenuates amyloidβ-induced synaptotoxicity by targeting calcium/calmodulin-dependent protein kinase kinase 2

The calcium/calmodulin-dependent protein kinase kinase 2, adenosine monophosphate-activated protein kinase (CAMKK2-AMPK) pathway mediated amyloid beta 42 (A beta 42)-induced synaptotoxicity and blockage of CAMKK2-protected neurons against the effect of A beta 42. Numerous microRNAs (miRNAs) were downregulated in response to A beta 42, including miR-9, a synapse-enriched miRNA that is decreased in Alzheimer's disease. In the present study the effect of miR-9 on A beta 42-triggered CAMKK2-AMPK activation and the synaptotoxic impairment was investigated. A beta 42 oligomers were identified to be capable of inducing CAMKK2-AMPK pathway activation, which was attenuated by miR-9 overexpression. CAMKK2 was predicted to be a target of miR-9 using Pictar and Targetscan 6.2 Bioinformatics' algorithms. A luciferase activity assay and western blot analysis confirmed that miR-9 significantly inhibited CAMKK2 expression. Additionally, overexpression of miR-9 was sufficient to restore A beta 42-induced dendritic spine loss and rescued A beta 42-induced tau phosphorylation at Ser-262 mediated by the CAMKK2-AMPK pathway. The results of the present study demonstrated that miR-9 attenuated A beta-induced synaptotoxicity by targeting CAMKK2.