3. Contribution of Insulin Resistance in Pathogenesis of Alzheimer Disease

  1. Tahira Farooqui and
  2. Akhlaq A. Farooqui
  1. Adnan Erol

Published Online: 11 OCT 2013

DOI: 10.1002/9781118395318.ch3

Metabolic Syndrome and Neurological Disorders

Metabolic Syndrome and Neurological Disorders

How to Cite

Erol, A. (2013) Contribution of Insulin Resistance in Pathogenesis of Alzheimer Disease, in Metabolic Syndrome and Neurological Disorders (eds T. Farooqui and A. A. Farooqui), John Wiley & Sons Ltd, Chichester, UK. doi: 10.1002/9781118395318.ch3

Author Information

  1. Erol Project Development House for the Disorders of Energy Metabolism, Silivri-Istanbul, Turkey

Publication History

  1. Published Online: 11 OCT 2013
  2. Published Print: 15 NOV 2013

ISBN Information

Print ISBN: 9781118395271

Online ISBN: 9781118395318

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Keywords:

  • β-catenin;
  • Alzheimer disease (AD);
  • AMP-activated protein kinase;
  • ataxia-telangiectasia mutated (ATM) signaling;
  • cyclin-dependent kinase (CDK) 5;
  • insulin resistance (IR);
  • insulin signaling pathway;
  • oxidative stress;
  • Wnt signaling pathway

Summary

This chapter discusses pathophysiological processes leading to insulin resistance (IR) in the central nervous system and their close association with Alzheimer related pathologies and addresses the probability of novel therapeutic opportunities. Several hypotheses were proposed to explain Alzheimer disease (AD) pathogenesis including: amyloid cascade excitotoxicity, oxidative stress, and inflammation. The formation of the β-catenin-TCF/LEF complex is the key event to the transcriptional regulation of target genes by the Wnt/β-catenin pathway. AMP-activated protein kinase (AMPK) pathway acts as a signal for ATP generation, a process coupled to increase in reactive oxygen species (ROS) production. Ataxia-telangiectasia mutated (ATM) activation are primarily viewed as a response to DNA damage, several recent studies have demonstrated that ATM can be activated independently from DNA damage through redox dependent mechanisms. Chronic hyperglycemia-induced deregulation of p35-Cyclin-dependent kinase (Cdk) 5 might be pathophysiological mechanism for the pancreatic β-cell dysfunction and apoptosis, leading to type 2 diabetes mellitus (T2D).