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

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 an...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 ObjectType-Feature-1
ISSN:	0197-4580 1558-1497
DOI:	10.1016/j.neurobiolaging.2009.04.016