title: Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players.
abstract: Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e.g. ceramide and products of advanced glycation) and ROS-modified cellular components, together with the activation of proapoptotic genes, could finally induce a suicide death program of autophagy/apoptosis in neurons. Recent studies reveal the impact of p53 on expression and processing of several microRNAs (miRs) under DNA damage-inducing conditions. Additionally, the role of miRs in promotion of insulin resistance and type 2 diabetes mellitus has been well documented. Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy.
authors.affiliation: Department of Basic Medical Sciences, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Gasiorowski
authors.affiliation: Department of Basic Medical Sciences, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brokos
authors.affiliation: Clinic of Psychiatry, Wrocław Medical University, Pasteura 10, 50-367 Wrocław, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Leszek
authors.affiliation: Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., 119991 Moscow. Russian Federation.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Tarasov
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ghulam Md
authors.initials: GM
authors.lastname: Ashraf
authors.affiliation: GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229. United States.|Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D004249:DNA Damage; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D035683:MicroRNAs / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53
keywords: Alzheimer disease; Insulin resistance; ROS; microRNAs; p53 protein