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P2–062: Binding of cholesterol to the C99 domain of APP competes with homodimerzation of the protein
Author(s) -
Song Yuanli,
Barrett Paul,
Van Horn Wade,
Hustedt Eric,
Sanders Charles
Publication year - 2013
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.2013.05.705
Subject(s) - popc , chemistry , transmembrane protein , transmembrane domain , amyloid precursor protein , biochemistry , cholesterol , biophysics , cleavage (geology) , lipid bilayer , amyloid precursor protein secretase , microbiology and biotechnology , biology , membrane , receptor , medicine , paleontology , disease , pathology , fracture (geology) , alzheimer's disease
AApeptide and also their potential on anti-Alzheimer’s diseases was evaluated.Methods: Herein, one bead one compound AApeptide library was designed for the selection of ligand that targets on Abeta. Selected AApeptides was evaluated for their effect on Aß1-40monomer peptides in their progress of aggregation. Methods are listed as follows: 1. Thioflavin T assay, ß-sheet formation assay for anti-aggregation screening. 2. TEM assay was used to image the morphological change of Aß fibrils with/without presence of AApeptide. 3. Western Blot, in vitro aggregation of HFIP treated Aß1-40 was produced to aggregate under room temperature, theformation of oligomers were detected using 6E10 anti-Aß antibodies. Following LI-COR western was used and quantification was performed for evaluation. Tissue culture, MTT assay on Neuroblastoma cell to test their toxicity. Kit using commercial available methods from Roche. Results: One of screened AApeptides shows great potential of anti-aggregation at concentration of 2.5mM at 1:1 ratio with Abeta. TEM assay also confirmed clearance of Aß fibrils in the presence of AApeptide. Toxicity of neuroblastma cells of AApeptide is not obvious at effective concentration. Conclusions: As a new generation of peptidomimetics, short AApeptide has great potential on Anti-Alzheimer’s diseases as an anti-aggregation drug.