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 β42 (Aβ42)-induced synaptotoxicity and blockage of CAMKK2-protected neurons against the effect of Aβ42. Numerous microRNAs (miRNAs) were downregulated in response to Aβ42, including miR-9, a synapse-enriched miRNA that is decreased in Alzheimer's disease. In the present study the effect of miR-9 on Aβ42‑triggered CAMKK2-AMPK activation and the synaptotoxic impairment was investigated. Aβ42 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 Aβ42-induced dendritic spine loss and rescued Aβ42-induced τ phosphorylation at Ser-262 mediated by the CAMKK2-AMPK pathway. The results of the present study demonstrated that miR-9 attenuated Aβ-induced synaptotoxicity by targeting CAMKK2.