Premium
O1‐05‐04: Exploring the effect of a change in plasma membrane cholesterol on the lipid rafts‐partitioning of APP using fluorescence correlation spectroscopy (FCS)
Author(s) -
Marquer Catherine,
Cossec JackChristophe,
Lécart Sandrine,
Liot Géraldine,
Humbert Sandrine,
Saudou Frédéric,
Duyckaerts Charles,
LévêqueFort Sandrine,
Potier MarieClaude
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.226
Subject(s) - lipid raft , cholera toxin , alexa fluor , chemistry , fluorescence correlation spectroscopy , microbiology and biotechnology , transmembrane protein , cholesterol , amyloid precursor protein , sphingomyelin , blot , biochemistry , membrane , lipid microdomain , biology , alzheimer's disease , fluorescence , receptor , medicine , endocrinology , physics , disease , organic chemistry , quantum mechanics , molecule , gene
Epitope mapping experiment using deletion mutants revealed that A5201A recognizes multiple regions in NCT, implicating that a mode of recognition of A5201A is conformation-dependent manner. Next we generated a scFv based on the variable region of A5201A. Intriguingly, the overexpression of A5201A-based scFv as an intrabody in mammalian cells suppressed the g-secretase activity. Biochemical analyses revealed that the scFv disrupted the proper folding and the appropriate glycosyl maturation of NCT, which are required for the stability of the g-secretase complex and the intrinsic proteolytic activity, respectively. Conclusions: These results provide compelling evidence that the extracellular domain of NCT can be a therapeutic target for Alzheimer’s disease through suppression of Ab generation.