title: Mechanisms of disease: new therapeutic strategies for Alzheimer's disease--targeting APP processing in lipid rafts.
abstract: 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.
authors.affiliation: University of Chicago, IL, USA.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Cheng
authors.forename: Kulandaivelu S
authors.initials: KS
authors.lastname: Vetrivel
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Xavier
authors.initials: X
authors.lastname: Meckler
authors.forename: Angèle
authors.initials: A
authors.lastname: Parent
authors.forename: Gopal
authors.initials: G
authors.lastname: Thinakaran
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human