MicroRNAS Role as Nuclear Factor Kappa B activator in Neurotrophin Pathway in Alzheimer's disease

MicroRNAS Role as Nuclear Factor Kappa B activator in Neurotrophin Pathway in Alzheimer's disease
setare samizade,^1,* Alireza Nasr Isfahani,² Anasik Karbedian hajiabadi,³ Fatemeh Abedi dorcheh,⁴
1. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
2. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
3. Department of Microbiology, School of Biological Sciences, Islamic Azad University of Falavarjan,Iran
4. Departman of Biotechnology,School of Bioscience and biotechnology,Shahid Ashrafi University Of Isfahan,Sepahan shahr,Iran
Introduction: Alzheimer's disease (AD) is a neurodegenerative with insidious onset and slow progression that nowadays impress more than 40 million people worldwide which is predicted to exponentially increase in the coming decades. AD is defined by the accumulation of dense plaques of β-amyloid peptide (Aβ) and neurofibrillary tangles of hyper phosphorylated tau that cause impairment in memory, cognition, and daily activities. The nuclear factor‐kappa β (NF‐κβ) plays an important role in the progression of AD. Recently, microRNAs (miRNAs) have emerged as a novel class of gene regulatory elements with conserved roles in development and disease .so the purpose of our study is to investigate the relationship between microRNAs and NF‐κβ in neurotrophin pathway.
Methods: The feature of microRNA was archived by using miRBase, HMDD and miRdSNP. Valid target genes and predict one were identified by miRTarBase, MIRWALK2.0, TargetScan and DIANA Tools. Venn diagram used to identify common target genes between MiRNAs .Gene expression in brain was obtained from The Human Protein Atlas. Finally, the pathway enrichment analysis was performed by the KEGG, David and ALZ path. GENEMANIA used to find gene network
Results: The result indicated that hsa-miR-1324, hsa-miR-185-5p, hsa-miR-199a-5p, hsa-miR-199b-5p, hsa-miR-24-3p and hsa-miR-573 inhibit MAPK3 by blocking RAS which active ERK5 and MEK5 by phosphorylation. Mentioned microRNAs activate NF‐κβ by inhibiting AKT, PDPK1 and PIK3CD in neurotrophin pathway and prevent Alzheimer development.
Conclusion: Factor nuclear factor-kappa B (NF‐κβ) is a key regulator of innate immunity, in the major genetic and environmental risk factor in neurotrophin pathway of AD. Finally hsa-miR-1324, hsa-miR-185-5p, hsa-miR-199a-5p, hsa-miR-199b-5p, hsa-miR-24-3p and hsa-miR-573 by acting as NF‐κβ activator, prevent Alzheimer progression.
Keywords: Alzheimer's disease, Neurotrophin, MicroRNA, NF‐κβ