General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases

被引:0
|
作者
Altintas, Ozlem [1 ]
MacArthur, Michael R. [1 ,2 ]
机构
[1] Swiss Fed Inst Technol, Dept Hlth Sci & Technol, Zurich, Switzerland
[2] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA
来源
FRONTIERS IN AGING | 2024年 / 5卷
关键词
GCN2; ISR; amino acids; aging; gerotherapeutic; geroprotection; cancer; AMINO-ACID DEPRIVATION; PROTEIN-KINASE GCN2; SENSOR GCN2; TRANSLATIONAL CONTROL; TRANSFER-RNA; T-CELLS; ACTIVATION; STRESS; BINDING; PHOSPHORYLATION;
D O I
10.3389/fragi.2024.1447370
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
The function of General Control Nonderepressible 2 (GCN2), an evolutionary-conserved component of the integrated stress response (ISR), has been well-documented across organisms from yeast to mammals. Recently GCN2 has also gained attention for its role in health and disease states. In this review, we provide a brief overview of GCN2, including its structure, activation mechanisms and interacting partners, and explore its potential significance as a therapeutic target in various age-related diseases including neurodegeneration, inflammatory disorders and cancer. Finally, we summarize the barriers to effectively targeting GCN2 for the treatment of disease and to promote a healthier aging process.
引用
收藏
页数:8
相关论文
共 50 条
  • [1] Role of General Control Nonderepressible 2 (GCN2) kinase in mediating responses to dietary methionine restriction
    Plaisance, Eric P.
    Van, Nancy
    Orgeron, Manda
    McDaniel, Alexandra N.
    Behrens, Phillip H.
    Gettys, Thomas W.
    Anthony, Tracy G.
    FASEB JOURNAL, 2012, 26
  • [2] General Control Nonderepressible 2 (GCN2) Kinase Inhibits Target of Rapamycin Complex 1 in Response to Amino Acid Starvation in Saccharomyces cerevisiae
    Yuan, Wenjie
    Guo, Shuguang
    Gao, Jiaoqi
    Zhong, Mingming
    Yan, Gonghong
    Wu, Wangmeng
    Chao, Yapeng
    Jiang, Yu
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (07) : 2660 - 2669
  • [3] Pulmonary vascular remodeling patterns and expression of general control nonderepressible 2 (GCN2) in pulmonary veno-occlusive disease
    Nossent, Esther J.
    Antigny, Fabrice
    Montani, David
    Bogaard, Harm Jan
    Ghigna, Maria Rosa
    Lambert, Melanie
    de Montpreville, Vincent Thomas
    Girerd, Barbara
    Jais, Xavier
    Savale, Laurent
    Mercier, Olaf
    Fadel, Elie
    Soubrier, Florent
    Sitbon, Olivier
    Simonneau, Gerald
    Noordegraaf, Anton Vonk
    Humbert, Marc
    Perros, Frederic
    Dorfmuller, Peter
    JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2018, 37 (05): : 647 - 655
  • [4] General Control Nonderepressible 2 (GCN2) Kinase Regulates Body Composition and Antioxidant Defenses during Dietary Methionine Restriction.
    Pettit, Ashley P.
    Bargoud, Albert
    Mirek, Emily T.
    Anthony, Tracy G.
    FASEB JOURNAL, 2016, 30
  • [5] The amino acid sensor general control nonderepressible 2 (GCN2) controls TH9 cells and allergic airway inflammation
    Wang, Peng
    Xu, Yana
    Zhang, Jiayu
    Shi, Lu
    Lei, Tong
    Hou, Yangxiao
    Lu, Zhongbing
    Zhao, Yong
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2019, 144 (04) : 1091 - 1105
  • [6] General Control Nonderepressible 2 (GCN2) Kinase Protects Oligodendrocytes and White Matter during Branched-chain Amino Acid Deficiency in Mice
    She, Pengxiang
    Bunpo, Piyawan
    Cundiff, Judy K.
    Wek, Ronald C.
    Harris, Robert A.
    Anthony, Tracy G.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (43) : 31250 - 31260
  • [7] Senescence as a therapeutic target in cancer and age-related diseases
    McHugh, Domhnall
    Duran, Imanol
    Gil, Jesus
    NATURE REVIEWS DRUG DISCOVERY, 2025, 24 (01) : 57 - 71
  • [8] Triazolo[4,5-d]pyrimidines as Validated General Control Nonderepressible 2 (GCN2) Protein Kinase Inhibitors Reduce Growth of Leukemia Cells
    Lough, Lea
    Sherman, Dan
    Becerra-Flores, Manuel
    Lavinda, Olga
    Ni, Eric
    Wang, Hong
    Tibes, Raoul
    Cardozo, Timothy
    COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, 2018, 16 : 350 - 360
  • [9] SIRT2 as a therapeutic target for age-related disorders
    de Oliveira, Rita Machado
    Sarkander, Jana
    Kazantsev, Aleksey G.
    Outeiro, Tiago Fleming
    FRONTIERS IN PHARMACOLOGY, 2012, 3
  • [10] Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review
    Mateo Amaya-Montoya
    Agustín Pérez-Londoño
    Valentina Guatibonza-García
    Andrea Vargas-Villanueva
    Carlos O. Mendivil
    Advances in Therapy, 2020, 37 : 1407 - 1424