Premium
P4‐170: Mechanistic studies of a bivalent compound containing curcumin and a membrane anchorage as a neuroprotectant in mc65 cell model
Author(s) -
Liu Kai,
Chojnacki Jeremy E.,
Saathoff John M.,
Wade Emily,
Yan Xing,
Zhang Shijun
Publication year - 2015
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.2015.06.1877
Subject(s) - viability assay , mtt assay , chemistry , annexin , apoptosis , microbiology and biotechnology , cell growth , intracellular , flow cytometry , biochemistry , biology
compounds in which the anionic terminus interacted with the cationic “H” residues of Ab and the cationic terminus interacted with the anionic “E” residue of Ab were identified. Although the standard alpha amino acids showed no capacity to inhibit Ab aggregation, a number of atypical amino acids including b-alanine, 2aminoethanesulfonic acid, and L-phosphoserine demonstrated varying capacities to inhibit the oligomerization and aggregation of Ab. These predictions were verified using in vitro assays, including the kinetic Thioflavin T [ThT] aggregation assay, to demonstrate the capacity of these compounds to inhibit misfolding. Conclusions: Searching for an “endogenous anti-AD compound” represents an unexplored concept. Our in silico and in vitro studies suggest that compounds endogenous to the human brain, including several zwitterionic small molecules, can inhibit pathological protein misfolding of Ab. The value of a novel in silico screening assay to identify bioactive endogenous agents within brain has also been demonstrated.