title: The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder which mainly affects elderly population. MicroRNAs (miRNA) are small RNA molecules that fine-tune gene expression at posttranscriptional level and exert important functions in AD. MicroRNA-124 (miR-124) is a kind of miRNA abundantly expressed in the central nervous system. It is highly conserved from Caenorhabditis elegans to humans. However, its function in AD is still elusive. In this study, we found miR-124 was significantly down-regulated in AD flies. miR-124 mutant flies showed impaired climbing ability and shortened lifespan. In contrast, miR-124 expression rescued locomotive defects of AD flies. Using microarray analysis to test gene expression profiles of miR-124 mutant flies, we found that Notch signaling pathway was potentially targeted by miR-124. Further experiments showed that miR-124 regulated Notch ligand Delta expression by acting on specific site of Delta 3`UTR. In addition, reduced Delta expression by RNA interference extended lifespan and ameliorated learning defects of AD Drosophila. Notch inhibitor DAPT could also alleviate AD phenotypes, which confirmed our findings. In conclusion, our study indicates that miR-124 plays neuroprotective roles in AD Drosophila by targeting Delta in Notch signaling pathway, which helps further our understanding of miRNAs in the molecular pathology of AD.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, 210009, Nanjing, China. kongyancn@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Wan
authors.forename: L
authors.initials: L
authors.lastname: Yuan
mesh_terms: D020413:3' Untranslated Regions; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001665:Binding Sites; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D008136:Longevity / Q000187:drug effects / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D004151:Dipeptides; D047908:Intracellular Signaling Peptides and Proteins; C572067:MIRN124 microRNA, Drosophila; D008565:Membrane Proteins; D035683:MicroRNAs; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D034741:RNA, Small Interfering; C064045:delta protein