Inflammatory risk factors and pathologies promoting Alzheimer’s disease progression: is RAGE the key?
Carmela Matrone1, Mehdi Djelloul2, Giulio Taglialatela3 and Lorena Perrone4
1Department of Biomedicine, University of Aarhus, Aarhus, Denmark, 2Stem Cell Laboratory for CNS Disease Modeling, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden, 3Department of Neuroscience and Cell Biology, Galveston, TK, USA and 4UMUC Europe, Heidelberg, Germany
Offprint requests to: Lorena Perrone, EA 7281 R2D2, Medical School, Auvergne University, Clermont-Ferrand, France. e-mail: firstname.lastname@example.org
Summary. Epidemiological studies reveal growing evidence that most cases of Alzheimer’s Disease (AD) likely involve a combination of genetic and environmental risk factors. Identifying and validating these risk factors remains one of the most critical scientific challenges. Several diseases appear to have strong implications for neurodegeneration leading to dementia. This risk encompasses different forms of cardiovascular disease, carotid atherosclerosis, history of hypertension or high cholesterol, Type II diabetes, stroke or transient ischemic attack and brain trauma. However, the molecular pathways that are common and central in the progression of these diseases and AD are not yet elucidated. Unveiling these critical mechanisms at the molecular level is necessary for the development of therapeutic strategies aimed at preventing AD progression. The Receptor for Advanced Glycation Endproducts (RAGE) plays a key role in all the diseases that represent a risk for AD. RAGE-mediated signaling also contributes to neurodegeneration in AD, suggesting that it may mediate the effect of risk factors in promoting AD. We will summarize the current knowledge on the role of RAGE in pathologies promoting AD and in AD progression. We will also provide evidence showing the relevance of RAGE-induced inflammation as a risk pathway that is implicated in AD pathophysiology. Histol Histopathol 30, 125-139 (2015)
Key words: Alzheimer Disease, Risk factors, RAGE, TXNIP, Inflammation