P53 functional inhibitors behaving like pifithrin-β counteract the Alzheimer peptide non-β-amyloid component effects in human SH-SY5Y cells.

ABSTRACT: Alzheimer's disease (AD) develops from a complex setting of genetic and biochemical alterations, including an increased level of p53 in the brain. Here, the robust and specific activation of p53 by the fibrillar non-β-amyloid component (NAC) of AD was demonstrated in human neuroblastoma SH-SY5Y cells. For the first time, the increase in the level of p53 target gene transcription, the cell cycle arrest, and the induction of apoptosis elicited by NAC were evidenced. These effects were counterbalanced by pifithrin-β, a small molecule interfering with the p53 functions. Using the structure of a pifithrin-β analogue as a reference, a pharmacophore-based virtual screening of the ZINC database was performed. Among the resulting hits, 20 druglike heterocyclic compounds were selected and evaluated

SUBMITTER: Da Pozzo E 

PROVIDER: S-EPMC4030802 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature