PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory

Mol Psychiatry. 2021 Sep;26(9):4968-4981. doi: 10.1038/s41380-021-01024-1. Epub 2021 Jan 28.


Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2MAPK signaling cascade strengthens memory. When stress is particularly intense, very high levels of glucocorticoid hormones then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. PAI-1 levels after trauma could be a predictive biomarker of the subsequent appearance of PTSD and pharmacological inhibition of PAI-1 activity a new therapeutic approach to this debilitating condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fear
  • Glucocorticoids
  • Hippocampus
  • Humans
  • Plasminogen Activator Inhibitor 1*
  • Stress Disorders, Post-Traumatic*


  • Glucocorticoids
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human