TY - JOUR
T1 - Insulin resistance in Alzheimer disease
T2 - Is heme oxygenase-1 an Achille's heel?
AU - Barone, Eugenio
AU - Butterfield, D. Allan
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/1/14
Y1 - 2015/1/14
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer disease
KW - Heme oxygenase
KW - Insulin resistance
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84924678620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924678620&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2015.02.013
DO - 10.1016/j.nbd.2015.02.013
M3 - Review article
C2 - 25731746
AN - SCOPUS:84924678620
SN - 0969-9961
VL - 84
SP - 69
EP - 77
JO - Neurobiology of Disease
JF - Neurobiology of Disease
ER -