Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Understanding a missing link in how antidepressants work

25.11.2015

Scientists discover a new way in which antidepressants work via the well-known stress protein FKBP51

Scientists at the Max Planck Institute of Psychiatry in Munich have now identified a new functional link between the established depression risk factor FKBP51 and epigenetic changes. This new link improves our understanding of how antidepressants work. It is hoped that as a result in the future we will be able to match pharmaceuticals so that they address more specific biological changes and, as such, will improve the chance of successful treatment thus helping the millions of treatment resistant patients.


Paroxetine was found to only decreased methylation when FKBP51 was present.

© MPI for Psychiatry, 2015

One in ten people will experience the stress-related disorder depression at some point in their lives. Unfortunately, only one third of patients will respond successfully to the medications that are currently available. This low response rate is in part due to our poor understanding of the mechanisms by which these antidepressants work.

Now scientists at the Max Planck Institute of Psychiatry in Munich have identified another mechanism by which these drugs might exert their effects and a link in the chain of how the environment can have an impact on our genetic material.

Stress mediates its biological effects through the steroid hormone cortisol, a so called stress hormone. Steroid hormones work by passing through the cell’s membrane and binding to intracellular receptors. This receptor-hormone complex then moves to the nucleus of the cell and binds to special areas of DNA, called hormone response elements. This binding to hormone response elements leads to gene transcription and the production of other proteins.

The protein FKBP51 belongs to the group of molecular chaperones which are able to modulate the affinity a hormone has for a receptor. The chaperone FKBP51 is a known regulator of stress-related receptors in the brain. As part of the stress response, cortisol binds to intracellular glucocorticoid receptors. However, these receptors are made inactive when they have the chaperone FKBP51 bound to them. As a result, cortisol is less likely to bind to the receptor and so the stress response mechanism is interrupted.

It is therefore unsurprising that that FKBP51 is a well established risk factor for stress-related disorders. FKBP51 has also been shown to determine how well a patient responds to antidepressant therapy and relate to the recurrence of depressive episodes. Successful antidepressant treatment is closely related to the recovery of stress hormone regulation, which in turn is modulated by FKBP51.

Another way that stress exerts its effects is through the attachment (called methylation) of chemical markings (so-called methyl groups) to our genetic material, resulting in a persistent alteration in the activity of genes. These epigenetic changes have been shown to be not only important in the etiology of stress-related disorders but also important in determining the response to treatment.

The scientists looked for evidence of a functional link between FKBP51 and DNMT1 in cells, mice and humans and found that indeed FKBP51 does mediate stress induced epigenetic change in DNMT1. FKBP51 changed phosphorylation, protein complexes and enzymatic activity of DNMT1 which in turn decreased global DNA methylation. “What was really interesting is that the antidepressant Paroxetine only decreased DNMT1 when in the presence of FKBP51” says Nils Gassen, first author of the study. The establishment of this functional link between DNMT1 and FKBP51 suggests a new role for chaperones with actions that go beyond protein production to the genome and epigenome.


Contact

Dr. Theo Rein
Project Group Leader

Max Planck Institute of Psychiatry, München
Phone: +49 89 30622-531

Email: theorein@psych.mpg.de

Dr. Anna Niedl
Press and Public Relations

Max Planck Institute of Psychiatry, München
Phone: +49 89 30622-263

Fax: +49 89 30622-370

Email: presse@psych.mpg.de


Original publication
Gassen NC, Fries GR, Zannas AS, Hartmann J, Zschocke J, Hafner K, Carrillo-Roa T, Steinbacher J, Preißinger SN, Hoeijmakers L, Knop M, Weber F, Kloiber S, Lucae S, Chrousos GP, Carell T, Ising M, Binder EB, Schmidt MV, Rüegg J and Rein T.

Chaperoning epigenetics: FKBProtein51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine.

Science Signaling (2015)

Dr. Theo Rein | Max Planck Institute of Psychiatry, München

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>