Mechanisms of disease: new therapeutic strategies for Alzheimer's disease--targeting APP processing in lipid rafts
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Nat Clin Pract Neurol. 2007 Jul;3(7):374-82
Cheng H, Vetrivel KS, Gong P, Meckler X, Parent A, Thinakaran G.
University of Chicago, IL, USA.
Alzheimer'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.
PubMed ID and Record
Nat Clin Pract Neurol. 2007 Jul;3(7):374-82
Cheng H, Vetrivel KS, Gong P, Meckler X, Parent A, Thinakaran G.
University of Chicago, IL, USA.
Alzheimer'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.
PubMed ID and Record
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