title: Substitution of membrane cholesterol with β-sitosterol promotes nonamyloidogenic cleavage of endogenous amyloid precursor protein.
abstract: Increasing evidence has linked membrane cholesterol to amyloid precursor protein (APP) processing. β-Sitosterol (BS) is one of the most common forms of plant sterols, with the structure very similar to that of cholesterol. Using HT22 mouse hippocampal cells, this study investigated whether the substitution of membrane cholesterol with BS influences APP metabolism. It was found that cholesterol/BS substitution promoted nonamyloidogenic processing of APP without affecting membrane fluidity. Additional experiments suggest that the effect of membrane BS on APP metabolism is associated with the migration of APP from lipid rafts toward non-raft regions. Given that dietary BS can enter the brain and accumulates in the plasma membrane of brain cells, these results suggest a potential use of BS in the prevention of Alzheimer's disease.
authors.affiliation: Department of Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
authors.forename: Jisheng
authors.initials: J
authors.lastname: Wang
authors.forename: Fengming
authors.initials: F
authors.lastname: Wu
authors.forename: Chun
authors.initials: C
authors.lastname: Shi
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011499:Protein Processing, Post-Translational; D012855:Sitosterols / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D012855:Sitosterols; C025473:gamma-sitosterol; D002784:Cholesterol
keywords: 2-hydroxypropyl-β-cyclodextrin; 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate; AD; APP; Alzheimer’s disease; Aβ; BACE-1; BS; CHAPS; DMEM; Dulbecco’s Minimum Essential Medium; ELISA; HPβCD; IgG–HRP; PBST; TMA–DPH; amyloid precursor protein; beta amyloid; cholesterol; enzyme-linked immunosorbent assay; immunoglobulin G–horseradish peroxidase; membrane fluidity; phosphate-buffered saline with Tween 20; trimethylamine–diphenylhexatriene; β-secretase-1; β-sitosterol