Proteostasis and resilience: on the interphase between individual's and intracellular stress

Trends Endocrinol Metab. 2022 May;33(5):305-317. doi: 10.1016/j.tem.2022.02.003. Epub 2022 Mar 22.


A long proportion of the population is resilient to the negative consequences of stress. Glucocorticoids resulting from endocrine responses to stress are essential adaptive mediators, but also drive alterations to brain function, negatively impacting neuronal connectivity, synaptic plasticity, and memory-related processes. Recent evidence has indicated that organelle function and cellular stress responses are relevant determinant of vulnerability and resistance to environmental stress. At the molecular level, a fundamental mechanism of cellular stress adaptation is the maintenance of proteostasis, which also have key roles in sustaining basal neuronal function. Here, we discuss recent evidence suggesting that proteostasis unbalance at the level of the endoplasmic reticulum, the main site for protein folding in the cell, represents a possible mechanistic link between individuals and cellular stress.

Keywords: cellular stress; hypothalamic–pituitary–adrenal axis; resilience; stress; unfolded protein response.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress* / physiology
  • Humans
  • Interphase
  • Neurons / metabolism
  • Proteostasis* / physiology
  • Unfolded Protein Response