Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer's Disease. Abyadeh, M, Tofigh, N, Hosseinian, S, Hasan, M, Amirkhani, A, Fitzhenry, MJ, Gupta, Veer, Chitranshi, N, Salekdeh, GH, Haynes, PA, Gupta, V, Shahpasand, K and Mirzaei, M 2022, Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer's Disease., Cells, vol. 11, no. 6, doi: 10.3390/cells11060987. Attached Files Name Description MIMEType Size Downloads Title Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer's Disease. Author(s) Abyadeh, M Tofigh, N Hosseinian, S Hasan, M Amirkhani, A Fitzhenry, MJ Gupta, Veer orcid.org/0000-0003-4989-0764 Chitranshi, N Salekdeh, GH Haynes, PA Gupta, V Shahpasand, K Mirzaei, M Journal name Cells Volume number 11 Issue number 6 Publisher p Place of publication Switzerland Publication date 2022-03-14 ISSN 2073-4409 Keyword(s) Alzheimer’s disease GABAergic synapse pathway differentially expressed genes retrograde endocannabinoid signaling Summary Alzheimer's disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippocampus, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes; hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs; ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets. Language eng DOI 10.3390/cells11060987 Indigenous content off Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30166477 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)   Connect to published version Go to link with your DU access privileges   Author URL Go to link with your DU access privileges   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Wed, 06 Apr 2022, 08:14:46 EST Wed, 06 Apr 2022, 08:49:47 EST Thu, 28 Apr 2022, 06:03:43 EST Fri, 29 Apr 2022, 23:43:57 EST Mon, 02 May 2022, 14:05:39 EST Thu, 05 May 2022, 23:36:01 EST Filtered Full Citation counts:   Cited 0 times in TR Web of Science Cited 0 times in Scopus Search Google Scholar Access Statistics: 5 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Wed, 06 Apr 2022, 08:14:46 EST