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Mechanisms of disease: new therapeutic strategies for Alzheimer s disease--targeting APP processing in lipid rafts Cheng H; Vetrivel KS; Gong P; Meckler X; Parent A; Thinakaran GNat Clin Pract Neurol 2007[Jul]; 3 (7): 374-82Alzheimer's disease (AD) is the most common cause of age-related dementia. Pathologically, AD is characterized by the deposition in the brain of amyloid-beta peptides derived from proteolysis of amyloid precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. A growing body of evidence implicates cholesterol and cholesterol-rich membrane microdomains in amyloidogenic processing of APP. Here, we review recent findings regarding the association of BACE1, gamma-secretase and APP in lipid rafts, and discuss potential therapeutic strategies for AD that are based on knowledge gleaned from the membrane environment that fosters APP processing.|Alzheimer Disease/*therapy[MESH]|Amyloid Precursor Protein Secretases/metabolism[MESH]|Amyloid beta-Protein Precursor/*metabolism[MESH]|Animals[MESH]|Aspartic Acid Endopeptidases/metabolism[MESH]|Humans[MESH]|Membrane Microdomains/*metabolism[MESH]|Protein Transport/physiology[MESH] |
