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.
Keywords: Alzheimer disease, Insulin resistance, microRNAs, p53 protein, ROS.
Current Topics in Medicinal Chemistry
Title:Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players
Volume: 17 Issue: 12
Author(s): Kazimierz Gasiorowski, Barbara Brokos, Jerzy Leszek, Vadim V. Tarasov, Ghulam Md Ashraf and Gjumrakch Aliev
Affiliation:
Keywords: Alzheimer disease, Insulin resistance, microRNAs, p53 protein, ROS.
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.
Export Options
About this article
Cite this article as:
Gasiorowski Kazimierz, Brokos Barbara, Leszek Jerzy, Tarasov V. Vadim, Ashraf Md Ghulam and Aliev Gjumrakch, Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players, Current Topics in Medicinal Chemistry 2017; 17 (12) . https://dx.doi.org/10.2174/1568026617666170103161233
DOI https://dx.doi.org/10.2174/1568026617666170103161233 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Demographic and Clinical Evaluation of Patients with Pancreatic Cancer in Mashhad University of Medical Sciences During 2002-2013
Current Cancer Therapy Reviews Angiotensin II Blockade and Renal Protection
Current Pharmaceutical Design Nearly Half of Uncontrolled Hypertensive Patients could be Controlled by High-dose Titration of Amlodipine in the Clinical Setting: The ACHIEVE Study
Current Hypertension Reviews Lipid Metabolism and Nutrient Partitioning Strategies
Current Drug Targets - CNS & Neurological Disorders Targeting Pain-evoking Transient Receptor Potential Channels for the Treatment of Pain
Current Neuropharmacology Pathophysiology and Therapeutics of Cardiovascular Disease in Metabolic Syndrome
Current Pharmaceutical Design Medicinal Chemistry Approaches for Glucokinase Activation to Treat Type 2 Diabetes
Current Medicinal Chemistry Strategies for the Assessment of Metabolic Profiles of Steroid Hormones in View of Diagnostics and Drug Monitoring: Analytical Problems and Challenges
Current Drug Metabolism Ezetimibe Therapy for Dyslipidemia: An Update
Current Pharmaceutical Design The Role of Polyunsaturated Fatty Acids (PUFA) in the Treatment of Dyslipidemias
Current Pharmaceutical Design Insight to the Pathophysiology of Stable Angina Pectoris
Current Pharmaceutical Design Therapeutic Effects of Melatonin On Liver And Kidney Damages In Intensive Exercise Model of Rats
Endocrine, Metabolic & Immune Disorders - Drug Targets Bioartificial Pancreas: Drug Delivery through Islet Microencapsulation to Treat Diabetes
Recent Patents on Biomedical Engineering (Discontinued) Discovery of 6-Deoxydapagliflozin as a Highly Potent Sodium-dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes
Medicinal Chemistry Comparison of Postpartum Hemoglobin and Hematocrit Levels In Conventional and Physiological Delivery in Iran: A Quasi-Experimental Study
Current Women`s Health Reviews Intravitreal Anti-VEGF Drugs as Adjuvant Therapy in Diabetic Retinopathy Surgery
Current Diabetes Reviews Circulatory Syndrome: An Evolution of the Metabolic Syndrome Concept!
Current Cardiology Reviews Biochemical Markers in the Prediction of Contrast-induced Acute Kidney Injury
Current Medicinal Chemistry High-Density Lipoprotein: Key Molecule in Cholesterol Efflux and the Prevention of Atherosclerosis
Current Pharmaceutical Design Differential Action of Phytochemicals on Platelet Apoptosis: A Biological Overview
Current Medicinal Chemistry