New research has uncovered how key proteins interact to regulate the body’s response to stress – a finding that could lead to new treatments for post-traumatic stress disorder (PTSD) and other stress-related psychiatric disorders.
New research carried out by McLean Hospital has detailed the interplay between proteins involved in controlling the body’s stress response, which researchers say could lead to potential therapeutic targets when this response goes awry.
To date, the biological mechanisms behind stress-related psychiatric conditions such as major depressive disorder and PTSD are poorly understood. The study, published in the journal Cell Reports, highlights that targeting these proteins may help treat or prevent stress-related disorders.
The interaction of proteins
The team carried out experiments in non-human tissue and post-mortem brain tissue which revealed how proteins including the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the FK506-binding protein 51 (FKBP5), interact with each other.
They found that MRs, rather than GRs, control the production of FKBP5 under normal conditions. FKBP5 decreases GRs’ sensitivity to binding stress hormones during stressful situations and appears to fine-tune the stress response by acting as a mediator of the MR:GR balance in the hippocampus.
Lead author Jakob Hartmann, PhD. Hartmann, Assistant Neuroscientist in the Neurobiology of Fear Laboratory at McLean and an instructor in psychiatry at Harvard Medical School, said: “A dysregulated stress response of the body can be damaging for the brain and promote susceptibility to mood and anxiety disorders.
“A key brain region involved in the regulation of the stress response is the hippocampus. The idea for this study occurred to us when we noticed interesting distinctions in hippocampal localisation of three important stress-regulating proteins.”
“Our findings suggest that therapeutic targeting of GR, MR, and FKBP5 may be complementary in manipulating central and peripheral regulation of stress,” added senior author Kerry J. Ressler, MD, PhD. Ressler is the Chief Scientific Officer at McLean Hospital, chief of McLean’s Division of Depression and Anxiety Disorders, and a professor in psychiatry at Harvard Medical School.
“Moreover, our data further underline the important but largely unappreciated role of MR signalling in stress-related psychiatric disorders,” added Ressler. “The findings of this study will open new directions for future research.”
