TY - JOUR
T1 - The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease
AU - Barone, Eugenio
AU - Di Domenico, Fabio
AU - Perluigi, Marzia
AU - Butterfield, D. Allan
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/11/20
Y1 - 2021/11/20
N2 - Alzheimer's disease (AD) is the most common form of dementia in the elderly followed by vascular dementia. In addition to clinically diagnosed dementia, cognitive dysfunction has been reported in diabetic patients. Recent studies are now beginning to recognize type 2 diabetes mellitus (T2DM), characterized by chronic hyperglycemia and insulin resistance, as a risk factor for AD and other cognitive disorders. While studies on insulin action have remained traditionally in the domain of peripheral tissues, the detrimental effects of insulin resistance in the central nervous system on cognitive dysfunction are increasingly being reported in recent clinical and preclinical studies. Brain functions require continuous supply of glucose and oxygen and a tight regulation of metabolic processes. Loss of this metabolic regulation has been proposed to be a contributor to memory dysfunction associated with neurodegeneration. Within the above scenario, this review will focus on the interplay among oxidative stress (OS), insulin resistance and AMPK dysfunctions in the brain by highlighting how these neurotoxic events contribute to neurodegeneration. We provide an overview on the detrimental effects of OS on proteins regulating insulin signaling and how these alterations impact cell metabolic dysfunctions through AMPK dysregulation. Such processes, we assert, are critically involved in the molecular pathways that underlie AD.
AB - Alzheimer's disease (AD) is the most common form of dementia in the elderly followed by vascular dementia. In addition to clinically diagnosed dementia, cognitive dysfunction has been reported in diabetic patients. Recent studies are now beginning to recognize type 2 diabetes mellitus (T2DM), characterized by chronic hyperglycemia and insulin resistance, as a risk factor for AD and other cognitive disorders. While studies on insulin action have remained traditionally in the domain of peripheral tissues, the detrimental effects of insulin resistance in the central nervous system on cognitive dysfunction are increasingly being reported in recent clinical and preclinical studies. Brain functions require continuous supply of glucose and oxygen and a tight regulation of metabolic processes. Loss of this metabolic regulation has been proposed to be a contributor to memory dysfunction associated with neurodegeneration. Within the above scenario, this review will focus on the interplay among oxidative stress (OS), insulin resistance and AMPK dysfunctions in the brain by highlighting how these neurotoxic events contribute to neurodegeneration. We provide an overview on the detrimental effects of OS on proteins regulating insulin signaling and how these alterations impact cell metabolic dysfunctions through AMPK dysregulation. Such processes, we assert, are critically involved in the molecular pathways that underlie AD.
KW - AMP-Activated protein kinase
KW - Alzheimer disease and type 2 diabetes
KW - Biliverdin reductase-A
KW - Insulin resistance
KW - Neurodegeneration
KW - Oxidative and nitrosative stress
UR - http://www.scopus.com/inward/record.url?scp=85114802429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114802429&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2021.09.006
DO - 10.1016/j.freeradbiomed.2021.09.006
M3 - Article
C2 - 34530075
AN - SCOPUS:85114802429
SN - 0891-5849
VL - 176
SP - 16
EP - 33
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -