Crosstalk between calcium, amyloid beta and the receptor for advanced glycation endproducts in Alzheimer's disease.
Hallmarks of Alzheimer's disease (AD) include the accumulation of amyloid beta peptide (Abeta), hyperphosphorylation of tau protein, and increased inflammatory activity in the hippocampus and cerebral cortex. The receptor for advanced glycation endproducts (RAGE) has been shown to interact with Abeta and to modulate Abeta transport across the blood-brain barrier. Furthermore, RAGE is upregulated at sites of inflammation and its activation results in distinct intracellular signaling cascades in respect to Abeta conformers. Besides Abeta, RAGE interacts with several members of the calcium binding S100 protein family, amphoterin and advanced glycation endproducts. Mounting evidence suggests that RAGE is a key player in the signaling pathways triggered by Abeta and S100 proteins in AD. In this review, we discuss recent discoveries about the crosstalk between RAGE, Abeta and S100 proteins in the pathophysiology of AD.
Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA. eleclerc@fau.edu
Estelle
E
Leclerc
Emmanuel
E
Sturchler
Stefan W
SW
Vetter
Claus W
CW
Heizmann
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D002118:Calcium