Matches in SemOpenAlex for { <https://semopenalex.org/work/W4306882651> ?p ?o ?g. }
- W4306882651 abstract "Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory and tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions aim at selectively eliminating senescent cells. In this study, a drug library screen uncovered TrkB (NTRK2) inhibitors capable of triggering apoptosis of several senescent, but not proliferating, human cells. Senescent cells expressed high levels of TrkB, which supported senescent cell viability, and secreted the TrkB ligand BDNF. The reduced viability of senescent cells after ablating BDNF signaling suggested an autocrine function for TrkB and BDNF, which activated ERK5 and elevated BCL2L2 levels, favoring senescent cell survival. Treatment with TrkB inhibitors reduced the accumulation of senescent cells in aged mouse organs. We propose that the activation of TrkB by SASP factor BDNF promotes cell survival and could be exploited therapeutically to reduce the senescent-cell burden." @default.
- W4306882651 created "2022-10-21" @default.
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- W4306882651 date "2022-10-20" @default.
- W4306882651 modified "2023-10-18" @default.
- W4306882651 title "A BDNF-TrkB autocrine loop enhances senescent cell viability" @default.
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- W4306882651 doi "https://doi.org/10.1038/s41467-022-33709-8" @default.
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