1. Targeting stress granules: A novel therapeutic strategy for human diseases
- Author
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Juan Li, Fei Wang, Cheng Huang, Zhigang Jin, and Shengjie Fan
- Subjects
0301 basic medicine ,FTD, frontotemporal dementia ,Aging ,ATF4, activating transcription factor 4 ,4E-BP1, eIF4E-binding protein 1 ,GCN4, general control non-derepressible 4 ,PKR, protein kinase RNA-activated ,SA, sodium arsenite ,TIA-1, T cell restricted intracellular antigen-1 ,eIF4F, eukaryotic initiation factor 4F ,TIAR-2, homolog of human TIA-1 inC. elegans pharyngeal muscles ,Disease ,Caprin 1, cell cycle associated protein 1 ,FUS/TLS, fused in sarcoma/translocated in liposarcoma ,Sorafenib (PubChem CID: 216239) ,Puromycin (PubChem CID: 439530) ,Pathogenesis ,G3BP ,0302 clinical medicine ,neurodegenerative disease ,ERK, extracellular signal-regulated kinase ,5-Fluorouracil (PubChem CID: 3385) ,Neoplasms ,HDAC, histone deacetylases ,virus infection ,PERK, PKR-like endoplasmatic reticulum kinase ,Chronic stress ,P-body, processing body ,HRI, heme-regulated inhibitor ,Psammaplysin F (PubChem CID: 46888580) ,Neurodegenerative Diseases ,ALS, amyotrophic lateral sclerosis ,ISRIB (PubChem CID: 1011240) ,Cell biology ,E)-3-(2,3,4,5-tetrabromophenyl)prop-2-enoic acid (PubChem CID: 16760346) ,PAI-1, plasminogen activator inhibitor-1 ,Virus Diseases ,030220 oncology & carcinogenesis ,JNK, c-Jun N-terminal kinase ,RBP, RNA-binding protein ,medicine.symptom ,DDX3X, DEAD box RNA helicase 3 X-linked ,NLRP3, NLR Family, Pyrin Domain Containing Protein 3 ,microtubule ,Signal Transduction ,TDP-43, TAR DNA binding protein 43 ,Olaparib (PubChem CID: 23725625) ,eIF2α ,Inflammation ,Antineoplastic Agents ,mTOR, mammalian target of rapamycin ,Biology ,LLPS, liquid-liquid phase separation ,AD, Alzheimer’s disease ,Cytoplasmic Granules ,Antiviral Agents ,Article ,eIF2, eukaryotic initiation factor 2 ,03 medical and health sciences ,Stress granule ,Eukaryotic translation ,ROS, reactive oxygen species ,stomatognathic system ,Stress, Physiological ,medicine ,Animals ,Humans ,RNA, Messenger ,ComputingMethodologies_COMPUTERGRAPHICS ,Pharmacology ,hsp, heat shock protein ,Messenger RNA ,GCN2, general control non-derepressible 2 ,Paclitaxel (PubChem CID: 36314) ,CK2, Casein kinase 2 ,Proteins ,G3BP1/2, Ras GTPase-activating protein-binding protein 1 and 2 ,SG, stress granule ,DOX, doxorubicin ,N protein, nucleocapsid protein ,VCP, valosin-containing protein ,030104 developmental biology ,post-translational modification ,Apoptosis ,Silvestrol (PubChem CID: 11787114) ,PP242 (PubChem CID:135565635) ,mRNP, messenger ribonucleoprotein ,5-FU, 5-fluorouracil ,Bortezomib (PubChem CID: 387447) ,PTM, post-translational modifications ,Trehalose (PubChem CID: 7427) - Abstract
Graphic abstract, Stress granules (SGs) are assemblies of mRNA and proteins that form from mRNAs stalled in translation initiation in response to stress. Chronic stress might even induce formation of cytotoxic pathological SGs. SGs participate in various biological functions including response to apoptosis, inflammation, immune modulation, and signalling pathways; moreover, SGs are involved in pathogenesis of neurodegenerative diseases, viral infection, aging, cancers and many other diseases. Emerging evidence has shown that small molecules can affect SG dynamics, including assembly, disassembly, maintenance and clearance. Thus, targeting SGs is a potential therapeutic strategy for the treatment of human diseases and the promotion of health. The established methods for detecting SGs provided ready tools for large-scale screening of agents that alter the dynamics of SGs. Here, we describe the effects of small molecules on SG assembly, disassembly, and their roles in the disease. Moreover, we provide perspective for the possible application of small molecules targeting SGs in the treatment of human diseases.
- Published
- 2020