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MicroRNA expression analysis of adult-onset Drosophila Alzheimer's disease model.
Curr Alzheimer Res. 2014; 11(9):882-91.CA

Abstract

Alzheimer's disease (AD) is the most common reason for dementia in elderly population. Its neuropathological features include senile plaques, neurofibril tangles and neuronal death. Scientists have established many AD animal models, including yeast, Caenorhabditis elegans, Drosophila melanogaster, mice, rats and non-human primates. Drosophila AD models are much more efficient for genetic manipulation and screening assay than mammals. microRNAs (miRNAs) are ~22nt small RNA molecules that fine-tune gene expression at posttranscriptional level. The dysregulation of miRNAs could participate in AD progression by influencing targets' expression and functions. However, miRNA expression profile of AD flies has not yet been investigated. Using the latest µParaflo™ miRNA microarray assay, we found that 17 miRNAs that were consistently dysregulated in adult-onset AD Drosophila brains: eight of which were upregulated (miR- 8, miR-13b, miR-277, miR-279, miR-981, miR-995, miR-998, miR-1017) and nine were downregulated (let-7, miR-1, miR-9a, miR-184, miR-193, miR-263b, miR-276a, miR-285, miR-289). KEGG pathway annotations using DIANA miRPath or targets predicted by Targetscan identified 7 pathways (Valine, leucine and isoleucine degradation; MAPK signaling pathway; Dorso-ventral axis formation; Propanoate metabolism; Sphingolipid metabolism; Lysine degradation; Jak- STAT signaling pathway) which might be influenced by these miRNAs. Integrative miRNA/mRNA regulatory network analysis revealed functional cluster with transaminase activity to be potentially regulated by miRNAs in AD. Taken together, our profiling assay identified miRNAs as markers for adult onset AD Drosophila. Dysregulation of miRNA profile may participate in AD pathogenesis by interrupting the metabolism of amino acids in the brain.

Authors+Show Affiliations

Kong Y
No affiliation info available
Wu J
No affiliation info available
Yuan L
Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu Province, 21009, China. kongyancn@gmail.com.

MeSH

Alzheimer DiseaseAnimalsAnimals, Genetically ModifiedAssociation LearningBrainCell LineConditioning, ClassicalDisease Models, AnimalDrosophila melanogasterElectroshockEnzyme-Linked Immunosorbent AssayFemaleMicroRNAsMicroarray AnalysisMotor ActivityOlfactory PerceptionRNA, MessengerReal-Time Polymerase Chain ReactionTransfection

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25274109

Citation

Kong, Yan, et al. "MicroRNA Expression Analysis of Adult-onset Drosophila Alzheimer's Disease Model." Current Alzheimer Research, vol. 11, no. 9, 2014, pp. 882-91.
Kong Y, Wu J, Yuan L. MicroRNA expression analysis of adult-onset Drosophila Alzheimer's disease model. Curr Alzheimer Res. 2014;11(9):882-91.
Kong, Y., Wu, J., & Yuan, L. (2014). MicroRNA expression analysis of adult-onset Drosophila Alzheimer's disease model. Current Alzheimer Research, 11(9), 882-91.
Kong Y, Wu J, Yuan L. MicroRNA Expression Analysis of Adult-onset Drosophila Alzheimer's Disease Model. Curr Alzheimer Res. 2014;11(9):882-91. PubMed PMID: 25274109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA expression analysis of adult-onset Drosophila Alzheimer's disease model. AU - Kong,Yan, AU - Wu,Jianban, AU - Yuan,Liudi, PY - 2014/06/18/received PY - 2014/08/20/revised PY - 2014/08/25/accepted PY - 2014/10/3/entrez PY - 2014/10/3/pubmed PY - 2015/7/24/medline SP - 882 EP - 91 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 11 IS - 9 N2 - Alzheimer's disease (AD) is the most common reason for dementia in elderly population. Its neuropathological features include senile plaques, neurofibril tangles and neuronal death. Scientists have established many AD animal models, including yeast, Caenorhabditis elegans, Drosophila melanogaster, mice, rats and non-human primates. Drosophila AD models are much more efficient for genetic manipulation and screening assay than mammals. microRNAs (miRNAs) are ~22nt small RNA molecules that fine-tune gene expression at posttranscriptional level. The dysregulation of miRNAs could participate in AD progression by influencing targets' expression and functions. However, miRNA expression profile of AD flies has not yet been investigated. Using the latest µParaflo™ miRNA microarray assay, we found that 17 miRNAs that were consistently dysregulated in adult-onset AD Drosophila brains: eight of which were upregulated (miR- 8, miR-13b, miR-277, miR-279, miR-981, miR-995, miR-998, miR-1017) and nine were downregulated (let-7, miR-1, miR-9a, miR-184, miR-193, miR-263b, miR-276a, miR-285, miR-289). KEGG pathway annotations using DIANA miRPath or targets predicted by Targetscan identified 7 pathways (Valine, leucine and isoleucine degradation; MAPK signaling pathway; Dorso-ventral axis formation; Propanoate metabolism; Sphingolipid metabolism; Lysine degradation; Jak- STAT signaling pathway) which might be influenced by these miRNAs. Integrative miRNA/mRNA regulatory network analysis revealed functional cluster with transaminase activity to be potentially regulated by miRNAs in AD. Taken together, our profiling assay identified miRNAs as markers for adult onset AD Drosophila. Dysregulation of miRNA profile may participate in AD pathogenesis by interrupting the metabolism of amino acids in the brain. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/25274109/MicroRNA_expression_analysis_of_adult_onset_Drosophila_Alzheimer's_disease_model_ DB - PRIME DP - Unbound Medicine ER -