Diverse maturity-dependent and complementary anti-apoptotic brakes safeguard human iPSC-derived neurons from cell death.

ABSTRACT: In humans, most neurons are born during embryonic development and have to persist throughout the entire lifespan of an individual. Thus, human neurons have to develop elaborate survival strategies to protect against accidental cell death. We set out to decipher the developmental adaptations resulting in neuronal resilience. We demonstrate that, during the time course of maturation, human neurons install a complex and complementary anti-apoptotic signaling network. This includes i.) a downregulation of central proteins of the intrinsic apoptosis pathway including several caspases, ii.) a shift in the ratio of pro- and anti-apoptotic BCL-2 family proteins, and iii.) an elaborate regulatory network resulting in upregulation of the inhibitor of apoptosis protein (IAP) XIAP. Together, these ada

SUBMITTER: Wilkens R 

PROVIDER: S-EPMC9587001 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature