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

被引:21
作者
Malekpour, Mahdi [1 ,2 ]
Shekouh, Dorsa [1 ]
Safavinia, Mohammad Ebrahim [1 ]
Shiralipour, Shadi [1 ]
Jalouli, Maryam [1 ]
Mortezanejad, Sahar [1 ]
Azarpira, Negar [2 ]
Ebrahimi, Niloofar Dehdari [2 ]
机构
[1] Shiraz Univ Med Sci, Student Res Comm, Shiraz, Iran
[2] Shiraz Univ Med Sci, Transplant Res Ctr, Shiraz, Iran
来源
FRONTIERS IN PSYCHIATRY | 2023年 / 14卷
关键词
FKBP5; psychiatric diseases; stress induced psychiatric disorders; genetic; drug discovery; PITUITARY-ADRENAL AXIS; GLUCOCORTICOID-RECEPTOR BINDING; HEAT-SHOCK-PROTEIN; CHILDHOOD TRAUMA; TREATMENT-RESISTANT; TREATMENT RESPONSE; MAJOR DEPRESSION; DNA METHYLATION; ANTIDEPRESSANT TREATMENT; HYPERACTIVITY DISORDER;
D O I
10.3389/fpsyt.2023.1182345
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
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页数:18
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共 214 条
  • [1] Antidepressant pharmacogenetics in children and young adults: A systematic review
    Al Maruf, Abdullah
    Greenslade, Alexandra
    Arnold, Paul D.
    Bousman, Chad
    [J]. JOURNAL OF AFFECTIVE DISORDERS, 2019, 254 : 98 - 108
  • [2] The Trier Social Stress Test: Principles and practice
    Allen, Andrew P.
    Kennedy, Paul J.
    Dockray, Samantha
    Cryan, John F.
    Dinan, Timothy G.
    Clarke, Gerard
    [J]. NEUROBIOLOGY OF STRESS, 2017, 6 : 113 - 126
  • [3] FKBP5 gene variants and borderline personality disorder
    Amad, Ali
    Ramoz, Nicolas
    Peyre, Hugo
    Thomas, Pierre
    Gorwood, Philip
    [J]. JOURNAL OF AFFECTIVE DISORDERS, 2019, 248 : 26 - 28
  • [4] Arlt S, 2013, CURR ALZHEIMER RES, V10, P72
  • [5] FKBP5 blockade may provide a new horizon for the treatment of stress-associated disorders: An in-silico study
    Asadi-Pooya, Ali A.
    Malekpour, Mahdi
    Zamiri, Bardia
    Kashkooli, Mohammad
    Firouzabadi, Negar
    [J]. EPILEPSIA OPEN, 2023, 8 (02) : 633 - 640
  • [6] Potential role of FKBP5 single-nucleotide polymorphisms in functional seizures
    Asadi-Pooya, Ali A. A.
    Simani, Leila
    Asadollahi, Marjan
    Rashidi, Fatemeh Sadat
    Ahmadipour, Ehsan
    Alavi, Afagh
    Roozbeh, Mehrdad
    Akbari, Nayyereh
    Firouzabadi, Negar
    [J]. EPILEPSIA OPEN, 2023, 8 (02) : 479 - 486
  • [7] Differences in Duloxetine Dosing Strategies in Smoking and Nonsmoking Patients: Therapeutic Drug Monitoring Uncovers the Impact on Drug Metabolism
    Augustin, Marc
    Schoretsanitis, Georgios
    Hiemke, Christoph
    Gruender, Gerhard
    Haen, Ekkehard
    Paulzen, Michael
    [J]. JOURNAL OF CLINICAL PSYCHIATRY, 2018, 79 (05)
  • [8] Modulating FKBP5/FKBP51 and autophagy lowers HTT (huntingtin) levels
    Bailus, Barbara J.
    Scheeler, Stephen M.
    Simons, Jesse
    Sanchez, Maria A.
    Tshilenge, Kizito-Tshitoko
    Creus-Muncunill, Jordi
    Naphade, Swati
    Lopez-Ramirez, Alejandro
    Zhang, Ningzhe
    Lakshika Madushani, Kuruwitage
    Moroz, Stanislav
    Loureiro, Ashley
    Schreiber, Katherine H.
    Hausch, Felix
    Kennedy, Brian K.
    Ehrlich, Michelle E.
    Ellerby, Lisa M.
    [J]. AUTOPHAGY, 2021, 17 (12) : 4119 - 4140
  • [9] Venlafaxine and sertraline does not affect the expression of genes regulating stress response in female MDD patients
    Banach, Ewa
    Szczepankiewicz, Aleksandra
    Leszczynska-Rodziewicz, Anna
    Pawlak, Joanna
    Dmitrzak-Weglarz, Monika
    Zaremba, Dorota
    Twarowska-Hauser, Joanna
    [J]. PSYCHIATRIA POLSKA, 2017, 51 (06) : 1029 - 1038
  • [10] Structure-Based Design of High-Affinity Macrocyclic FKBP51 Inhibitors
    Bauder, Michael
    Meyners, Christian
    Purder, Patrick L.
    Merz, Stephanie
    Sugiarto, Wisely Oki
    Voll, Andreas M.
    Heymann, Tim
    Hausch, Felix
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (06) : 3320 - 3349