title: microRNA-9 attenuates amyloidβ-induced synaptotoxicity by targeting calcium/calmodulin-dependent protein kinase kinase 2.
abstract: 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.
authors.affiliation: Department of Neurology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chang
authors.affiliation: Department of Neurology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Lin-Hong
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Wu-Ping
authors.initials: WP
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jing
authors.affiliation: Department of Neurology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
authors.forename: Pei-Yan
authors.initials: PY
authors.lastname: Zhan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D035683:MicroRNAs; D012333:RNA, Messenger; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases