Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease

• Published in: Neurobiology of aging Vol. 32; no. 5; pp. 763 - 777
• Main Authors: Srikanth, Velandai, Maczurek, Annette, Phan, Thanh, Steele, Megan, Westcott, Bernadette, Juskiw, Damian, Münch, Gerald
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.05.2011; Elsevier
• Subjects: Advanced glycation endproducts; Aging - drug effects; Aging - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - epidemiology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Disease Progression; Fundamental and applied biological sciences. Psychology; Glycation; Glycation End Products, Advanced - antagonists & inhibitors; Glycation End Products, Advanced - chemistry; Glycation End Products, Advanced - metabolism; Humans; Inflammation; Internal Medicine; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Microglia - drug effects; Microglia - metabolism; Neurofibrillary Tangles - metabolism; Neurology; Nitric oxide; Oxidative Stress; Plaque, Amyloid - drug therapy; Plaque, Amyloid - metabolism; RAGE; Receptor for Advanced Glycation End Products; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - metabolism; Soluble RAGE; Vertebrates: nervous system and sense organs; β-Amyloid; methylglyoxal linked dimmer; M-CSF; carboxymethyl-lysine; interleukin-6; Aβ; BSA; NF-κB; β-secretase; iNOS; Alzheimer's disease; NFT; CAA; AD; CML; Maillard reaction products; nicotinamide adenine dinucleotide phosphate; PKC; β-amyloid peptide; MRPs; IL-6; BACE1; nuclear factor-κB; tumour necrosis factor-α; Nitric oxide; ROS; β-Amyloid; MAP; bovine serum albumin; MOLD; NADPH; PHFs; Oxidative stress; macrophage-colony stimulating factor; neurofibrillary tangles; advanced glycation endproducts; Glycation; inducible nitric oxide synthase; cerebral amyloid angiopathy; reactive oxygen species; protein kinase C; receptor for advanced glycation endproducts; AGEs; Inflammation; RAGE; paired helical filaments; Soluble RAGE; microtubule associated protein; TNF-α; Diabetes; Advanced glycation endproducts; Endocrinopathy; Nervous system diseases; Senescence; Alzheimer disease; Diabetes mellitus; Reaction product; RAGE receptor; Cerebral disorder; β Amyloid protein; Central nervous system disease; Degenerative disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2009.04.016

Abstract Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we revisit the hypothesis that advanced glycation endproducts (AGEs) and their receptor RAGE may play an important role in disease pathogenesis. Accumulation of AGEs in cells and tissues is a normal feature of aging, but is accelerated in AD. In AD, AGEs can be detected in pathological deposits such as amyloid plaques and neurofibrillary tangles. AGEs explain many of the neuropathological and biochemical features of AD such as extensive protein crosslinking, glial induction of oxidative stress and neuronal cell death. Oxidative stress and AGEs initiate a positive feedback loop, where normal age-related changes develop into a pathophysiological cascade. RAGE and its decoy receptor soluble RAGE, may contribute to or protect against AD pathogenesis by influencing transport of β-amyloid into the brain or by manipulating inflammatory mechanisms. Targeted pharmacological interventions using AGE-inhibitors, RAGE-antagonists, RAGE-antibodies, soluble RAGE or RAGE signalling inhibitors such as membrane-permeable antioxidants may be promising therapeutic strategies to slow down the progression of AD.