Insulin signaling, glucose metabolism and mitochondria: Major players in Alzheimer's disease and diabetes interrelation

• Published in: Brain research 2012-03, Vol.1441, p.64-78
• Main Authors: Correia, Sónia C, Santos, Renato X, Carvalho, Cristina, Cardoso, Susana, Candeias, Emanuel, Santos, Maria S, Oliveira, Catarina R, Moreira, Paula I
• Format: Article
• Language: English
• Subjects: Alzheimer disease; Alzheimer Disease - epidemiology; Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; brain; Cerebral glucose metabolism; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - metabolism; epidemiological studies; glucose; Glucose - metabolism; Glucose - physiology; Humans; insulin; Insulin - adverse effects; Insulin - metabolism; Insulin - physiology; insulin resistance; Insulin signaling; metabolism; Mitochondria; Mitochondria - physiology; Neurology; noninsulin-dependent diabetes mellitus; Oxidative stress; proteins; risk; Risk Factors; Signal Transduction - physiology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.12.063

Many epidemiological studies have shown that diabetes, particularly type 2 diabetes, significantly increases the risk to develop Alzheimer's disease. Both diseases share several common abnormalities including impaired glucose metabolism, increased oxidative stress, insulin resistance and deposition of amyloidogenic proteins. It has been suggested that these two diseases disrupt common cellular and molecular pathways and each disease potentiates the progression of the other. This review discusses clinical and biochemical features shared by Alzheimer's disease and diabetes, giving special attention to the involvement of insulin signaling, glucose metabolism and mitochondria. Understanding the key mechanisms underlying this deleterious interaction may provide opportunities for the design of effective therapeutic strategies.