Histone deacetylase inhibition expands cellular proteostasis repertoires to enhance neuronal stress resilience.

ABSTRACT: Neurons are long-lived, terminally differentiated cells with limited regenerative capacity. Cellular stressors such as endoplasmic reticulum (ER) protein folding stress and membrane trafficking stress accumulate as neurons age and accompany age-dependent neurodegeneration. Current strategies to improve neuronal resilience are focused on using factors to reprogram neurons or targeting specific proteostasis pathways. We discovered a different approach. In an unbiased screen for modifiers of neuronal membrane trafficking defects, we unexpectedly identified a role for histone deacetylases (HDACs) in limiting cellular flexibility in choosing cellular pathways to respond to diverse types of stress. Genetic or pharmacological inactivation of HDACs resulted in improved neuronal health in response

SUBMITTER: Taylor CA 

PROVIDER: S-EPMC11370365 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature