Document Detail


AGEs/RAGE complex upregulates BACE1 via NF-κB pathway activation.
MedLine Citation:
PMID:  20638753     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Although the pathogenesis of sporadic Alzheimer disease (AD) is not clearly understood, it is likely dependent on several age-related factors. Diabetes is a risk factor for AD, and multiple mechanisms connecting the 2 diseases have been proposed. Hyperglycemia enhances the formation of advanced glycation end products (AGEs) that result from the auto-oxidation of glucose and fructose. The interaction of AGEs with their receptor, named RAGE, elicits the formation of reactive oxygen species that are also believed to be an early event in AD pathology. To investigate a functional link between the disorders diabetes and AD, the effect of 2 AGEs, pentosidine and glyceraldehydes-derived pyridinium (GLAP), was studied on BACE1 expression both in vivo, in streptozotocin treated rats, and in vitro in differentiated neuroblastoma cells. We showed that pentosidine and GLAP were able to upregulate BACE1 expression through their binding with RAGE and the consequent activation of NF-κB. In addition, both pentosidine and GLAP were found to be increased in the brain in sporadic AD patients. Our findings demonstrate that activation of the AGEs/RAGE axis, by upregulating the key enzyme for amyloid-β production, provides a pathologic link between diabetes mellitus and AD.
Authors:
Michela Guglielmotto; Manuela Aragno; Elena Tamagno; Ilenia Vercellinatto; Sonia Visentin; Claudio Medana; Maria Graziella Catalano; Mark A Smith; George Perry; Oliviero Danni; Giuseppe Boccuzzi; Massimo Tabaton
Related Documents :
17021373 - Blood-brain barrier and energy balance.
15481723 - Optimal blood glucose levels while using insulin to minimize the size of infarction in ...
11007073 - Uptake and dispersion of metformin in the isolated perfused rat liver.
Publication Detail:
Type:  Journal Article     Date:  2010-07-17
Journal Detail:
Title:  Neurobiology of aging     Volume:  33     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  196.e13-27     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Experimental Medicine and Oncology, University of Turin, Turin, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Does microbial resistance or adaptation to biocides create a hazard in infection prevention and cont...
Next Document:  [Dyslipidemia and cardiovascular risk in the adult population of Castile-Leon (Spain)].