Cargando…

Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery

Stress-induced mental health disorders are affecting many people around the world. However, effective drug therapy for curing psychiatric diseases does not occur sufficiently. Many neurotransmitters, hormones, and mechanisms are essential in regulating the body's stress response. One of the mos...

Descripción completa

Detalles Bibliográficos
Autores principales: Malekpour, Mahdi, Shekouh, Dorsa, Safavinia, Mohammad Ebrahim, Shiralipour, Shadi, Jalouli, Maryam, Mortezanejad, Sahar, Azarpira, Negar, Ebrahimi, Niloofar Dehdari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313426/
https://www.ncbi.nlm.nih.gov/pubmed/37398599
http://dx.doi.org/10.3389/fpsyt.2023.1182345
_version_ 1785067125884321792
author Malekpour, Mahdi
Shekouh, Dorsa
Safavinia, Mohammad Ebrahim
Shiralipour, Shadi
Jalouli, Maryam
Mortezanejad, Sahar
Azarpira, Negar
Ebrahimi, Niloofar Dehdari
author_facet Malekpour, Mahdi
Shekouh, Dorsa
Safavinia, Mohammad Ebrahim
Shiralipour, Shadi
Jalouli, Maryam
Mortezanejad, Sahar
Azarpira, Negar
Ebrahimi, Niloofar Dehdari
author_sort Malekpour, Mahdi
collection PubMed
description Stress-induced mental health disorders are affecting many people around the world. However, effective drug therapy for curing psychiatric diseases does not occur sufficiently. Many neurotransmitters, hormones, and mechanisms are essential in regulating the body's stress response. One of the most critical components of the stress response system is the hypothalamus-pituitary-adrenal (HPA) axis. The FKBP prolyl isomerase 51 (FKBP51) protein is one of the main negative regulators of the HPA axis. FKBP51 negatively regulates the cortisol effects (the end product of the HPA axis) by inhibiting the interaction between glucocorticoid receptors (GRs) and cortisol, causing reduced transcription of downstream cortisol molecules. By regulating cortisol effects, the FKBP51 protein can indirectly regulate the sensitivity of the HPA axis to stressors. Previous studies have indicated the influence of FKBP5 gene mutations and epigenetic changes in different psychiatric diseases and drug responses and recommended the FKBP51 protein as a drug target and a biomarker for psychological disorders. In this review, we attempted to discuss the effects of the FKBP5 gene, its mutations on different psychiatric diseases, and drugs affecting the FKBP5 gene.
format Online
Article
Text
id pubmed-10313426
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-103134262023-07-01 Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery Malekpour, Mahdi Shekouh, Dorsa Safavinia, Mohammad Ebrahim Shiralipour, Shadi Jalouli, Maryam Mortezanejad, Sahar Azarpira, Negar Ebrahimi, Niloofar Dehdari Front Psychiatry Psychiatry Stress-induced mental health disorders are affecting many people around the world. However, effective drug therapy for curing psychiatric diseases does not occur sufficiently. Many neurotransmitters, hormones, and mechanisms are essential in regulating the body's stress response. One of the most critical components of the stress response system is the hypothalamus-pituitary-adrenal (HPA) axis. The FKBP prolyl isomerase 51 (FKBP51) protein is one of the main negative regulators of the HPA axis. FKBP51 negatively regulates the cortisol effects (the end product of the HPA axis) by inhibiting the interaction between glucocorticoid receptors (GRs) and cortisol, causing reduced transcription of downstream cortisol molecules. By regulating cortisol effects, the FKBP51 protein can indirectly regulate the sensitivity of the HPA axis to stressors. Previous studies have indicated the influence of FKBP5 gene mutations and epigenetic changes in different psychiatric diseases and drug responses and recommended the FKBP51 protein as a drug target and a biomarker for psychological disorders. In this review, we attempted to discuss the effects of the FKBP5 gene, its mutations on different psychiatric diseases, and drugs affecting the FKBP5 gene. Frontiers Media S.A. 2023-06-16 /pmc/articles/PMC10313426/ /pubmed/37398599 http://dx.doi.org/10.3389/fpsyt.2023.1182345 Text en Copyright © 2023 Malekpour, Shekouh, Safavinia, Shiralipour, Jalouli, Mortezanejad, Azarpira and Ebrahimi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Malekpour, Mahdi
Shekouh, Dorsa
Safavinia, Mohammad Ebrahim
Shiralipour, Shadi
Jalouli, Maryam
Mortezanejad, Sahar
Azarpira, Negar
Ebrahimi, Niloofar Dehdari
Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
title Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
title_full Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
title_fullStr Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
title_full_unstemmed Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
title_short Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
title_sort role of fkbp5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313426/
https://www.ncbi.nlm.nih.gov/pubmed/37398599
http://dx.doi.org/10.3389/fpsyt.2023.1182345
work_keys_str_mv AT malekpourmahdi roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT shekouhdorsa roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT safaviniamohammadebrahim roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT shiralipourshadi roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT jaloulimaryam roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT mortezanejadsahar roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT azarpiranegar roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery
AT ebrahiminiloofardehdari roleoffkbp5anditsgeneticmutationsinstressinducedpsychiatricdisordersanopportunityfordrugdiscovery