Insulin resistance in Alzheimer disease: Is heme oxygenase-1 an Achille's heel?

Eugenio Barone, D. Allan Butterfield

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


Insulin resistance, clinically defined as the inability of insulin to increase glucose uptake and utilization, has been found to be associated with the progression of Alzheimer disease (AD). Indeed, postmortem AD brain shows all the signs of insulin resistance including: (i) reduced brain insulin receptor (IR) sensitivity, (ii) hypophosphorylation of the insulin receptor and downstream second messengers such as IRS-1, and (iii) attenuated insulin and insulin growth factor (IGF)-1 receptor expression. However, the exact mechanisms driving insulin resistance have not been completely elucidated. Quite recently, the levels of the peripheral inducible isoform of heme oxygenase (HO-1), a well-known protein up-regulated during cell stress response, were proposed to be among the strongest positive predictors of metabolic disease, including insulin resistance. Because our group previously reported on levels, activation state and oxidative stress-induced post-translational modifications of HO-1 in AD brain and our ongoing studies to better elucidate the role of HO-1 in insulin resistance-associated AD pathology, the aim of this review is to provide reader with a critical analysis on new aspects of the interplay between HO-1 and insulin resistance and on how the available lines of evidence could be useful for further comprehension of processes in AD brain.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalNeurobiology of Disease
StatePublished - Jan 14 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.


  • Aging
  • Alzheimer disease
  • Heme oxygenase
  • Insulin resistance
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology


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