Fig. 1: Screening of a library of drugs directed at MAPK signaling proteins unveils Trk inhibitors as potential senolytic compounds.
From: A BDNF-TrkB autocrine loop enhances senescent cell viability
a Overview of the experimental strategy of the survey. Briefly, senescent and proliferating WI-38 and BJ fibroblasts were treated for 48 h with a collection of MAPK inhibitors, whereupon cell viability was assessed. b Schematic representation of the protocol used to reach full senescence using etoposide (Etop, 25 and 50 μM for BJ and WI-38 cells, respectively) for 10 days, refreshing etoposide twice, before treating the cell cultures with each of the drugs in the library for an additional 48 h; created using BioRender. c Bar plot displaying the % change of proliferating and senescent WI-38 fibroblasts (top graph) and BJ fibroblasts (bottom graph) after treatment with the drug library for 48 h (day 12) relative to the time before drug addition (day 10). Red line, percentages of cells present at each condition right before starting the treatments at day 10. All the drugs were added at a concentration of 10 μM. d Heat map representing the percentage of senolysis (percentage of cell death) after 48 h when comparing day 12 to day 10 in senescent cells. Drugs were grouped by the target proteins inhibited within the MAPK superfamily. Graphs in c represent the mean values ±SD of n = 3 experiments. See also Supplementary Fig. 1.
