The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5′Untranslated-Region-Directed Translation Blockers of the Parkinson’s Alpha Synuclein Expression
Figure 3
Posiphen is a stereospecific inhibitor of alpha synuclein 5′UTR-directed translation. Transient transfection assays with the SNCA-5′UTR-pGL3 construct (H2A cell line). Posiphen was a highly selective inhibitor (10 μM) of -synuclein 5′UTR-driven expression of a luciferase reporter gene. This stereoisomer of phenserine inhibited -synuclein 5′UTR-driven luciferase expression in neural cells (SNCA 5′UTR-positive transfected neural cells ()). By contrast, phenserine and the known APP-specific translation number 9 blocker did not suppress alpha synuclein 5′UTR-conferred translation in H2A cells. Phenserine and APP blocker number 9 increased SNCA 5′UTR-conferred translation. These data support the mechanism-of-action of posiphen as a highly selective blocker of alpha synuclein 5′UTR activity, whereas phenserine (same chemical structure but stereoisomer of posiphen) was previously shown selectively inhibiting translation driven by the APP 5′UTR.
