title: Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease.
abstract: Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia ; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, Perth, WA 6027, Australia.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Verdile
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Keane
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia ; Department of Physiology and Biophysics, Institute of Biomedical Sciences (ICB-I), University of São Paulo (USP), Avenida Prof. Lineu Prestes 1524, Butantã, 05508-000 São Paulo, SP, Brazil.
authors.forename: Vinicius F
authors.initials: VF
authors.lastname: Cruzat
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Medic
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia.
authors.forename: Miheer
authors.initials: M
authors.lastname: Sabale
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Rowles
authors.affiliation: University of Toronto, Tanz Centre for Research in Neurodegenerative Diseases, Department of Medical Biophysics, Krembil Discovery Tower, 60 Leonard Avenue, Toronto, ON, Canada M5T 2S8.
authors.forename: Nadeeja
authors.initials: N
authors.lastname: Wijesekara
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, Perth, WA 6027, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: University of Toronto, Tanz Centre for Research in Neurodegenerative Diseases, Department of Medical Biophysics, Krembil Discovery Tower, 60 Leonard Avenue, Toronto, ON, Canada M5T 2S8.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Newsholme
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051547:Heme Oxygenase-1 / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000150:complications*; D007333:Insulin Resistance; D009249:NADP / Q000378:metabolism; D009765:Obesity / Q000209:etiology*; D018384:Oxidative Stress; D019892:eIF-2 Kinase / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D009249:NADP; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D000071679:Glycogen Synthase Kinase 3 beta; D019892:eIF-2 Kinase; D038362:Glycogen Synthase Kinase 3