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Targeting stress granules: A novel therapeutic strategy for human diseases

Authors :
Juan Li
Fei Wang
Cheng Huang
Zhigang Jin
Shengjie Fan
Source :
Pharmacological Research
Publication Year :
2020
Publisher :
Elsevier Ltd., 2020.

Abstract

Graphic abstract<br />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.

Subjects

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)

Details

Language :
English
ISSN :
10961186 and 10436618
Database :
OpenAIRE
Journal :
Pharmacological Research
Accession number :
edsair.doi.dedup.....b80e1d4bdb2336a5aaab712b58bc9286