Ana Paula Mendes-Silva1, Kelly Silva Pereira1, Gesiane Thamire Tolentino-Araujo1, Eduardo de Souza Nicolau1, Camila Moreira Silva-Ferreira1, Antonio Lucio Teixeira2, Breno S Diniz3. 1. Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil. 2. Department of Psychiatry and Behavioral Sciences, University of Texas Medical Science Center at Houston, Houston, TX. 3. Graduate Program in Molecular Medicine, Federal University of Minas Gerais School of Medicine, Belo Horizonte, MG, Brazil; Department of Psychiatry and Behavioral Sciences, University of Texas Medical Science Center at Houston, Houston, TX. Electronic address: brenosatler@gmail.com.
Abstract
OBJECTIVE: The clinical-epidemiological relationship between major depressive disorder (MDD) and Alzheimer disease (AD) suggests that they may share common neurobiologic abnormalities. METHODS: The authors conducted a systematic review and identified microRNAs abnormally expressed in both AD and MDD. The pattern of microRNA regulation in each disorder and the genes regulated by each microRNA and the biologic processes and pathways regulated by these genes were identified. RESULTS: Seventy-four microRNAs were abnormally expressed in AD and 30 in MDD; 7 were common for both disorders (hsa-let-7f-5p, hsa-miR-664a-3p, hsa-miR-361-5p, hsa-let-7g-5p, hsa-let-7d-5p, hsa-miR-191-5p, hsa-miR-26b-5p). These microRNAs interact with 45 validated genes, and the main biologic pathways and processes regulated by them were proteostasis control, maintenance of genomic integrity, regulation of transcriptional activity, immune-inflammatory control, and neurotrophic support. CONCLUSION: The current results suggest that the maintenance of genomic integrity, proteostasis control, immune-inflammatory regulation, and neurotrophic support are key neurobiologic links between these conditions. A comprehensive hypothetical model for the interaction between MDD, aging, and the development of AD is provided.
OBJECTIVE: The clinical-epidemiological relationship between major depressive disorder (MDD) and Alzheimer disease (AD) suggests that they may share common neurobiologic abnormalities. METHODS: The authors conducted a systematic review and identified microRNAs abnormally expressed in both AD and MDD. The pattern of microRNA regulation in each disorder and the genes regulated by each microRNA and the biologic processes and pathways regulated by these genes were identified. RESULTS: Seventy-four microRNAs were abnormally expressed in AD and 30 in MDD; 7 were common for both disorders (hsa-let-7f-5p, hsa-miR-664a-3p, hsa-miR-361-5p, hsa-let-7g-5p, hsa-let-7d-5p, hsa-miR-191-5p, hsa-miR-26b-5p). These microRNAs interact with 45 validated genes, and the main biologic pathways and processes regulated by them were proteostasis control, maintenance of genomic integrity, regulation of transcriptional activity, immune-inflammatory control, and neurotrophic support. CONCLUSION: The current results suggest that the maintenance of genomic integrity, proteostasis control, immune-inflammatory regulation, and neurotrophic support are key neurobiologic links between these conditions. A comprehensive hypothetical model for the interaction between MDD, aging, and the development of AD is provided.
Authors: Thomas S Wingo; Jingjing Yang; Wen Fan; Se Min Canon; Ekaterina Sergeevna Gerasimov; Adriana Lori; Benjamin Logsdon; Bing Yao; Nicholas T Seyfried; James J Lah; Allan I Levey; Patricia A Boyle; Julia A Schneider; Philip L De Jager; David A Bennett; Aliza P Wingo Journal: NPJ Genom Med Date: 2020-02-06 Impact factor: 8.617
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