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

Srikanth, Velandai, Maczurek, Annette, Phan, Thanh, Steele, Megan, Westcott, Bernadette, Juskiw, Damian, and Münch, Gerald (2011) Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease. Neurobiology of Aging, 32 (5). pp. 763-777.

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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.

Item ID: 21829
Item Type: Article (Refereed Research - C1)
ISSN: 1558-1497
Date Deposited: 10 May 2012 00:21
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110102 Medical Biochemistry: Carbohydrates @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920112 Neurodegenerative Disorders Related to Ageing @ 100%
Citation Count from Web of Science Web of Science 2
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