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