Elsevier

Pharmacological Research

Volume 161, November 2020, 105143
Pharmacological Research

Review
Targeting stress granules: A novel therapeutic strategy for human diseases

https://doi.org/10.1016/j.phrs.2020.105143Get rights and content

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.

Abbreviation

AD
Alzheimer’s disease
ALS
amyotrophic lateral sclerosis
ATF4
activating transcription factor 4
Caprin 1
cell cycle associated protein 1
CK2
Casein kinase 2
DDX3X
DEAD box RNA helicase 3 X-linked
DOX
doxorubicin
eIF2
eukaryotic initiation factor 2
eIF4F
eukaryotic initiation factor 4F
ERK
extracellular signal-regulated kinase
FTD
frontotemporal dementia
FUS/TLS
fused in sarcoma/translocated in liposarcoma
GCN2
general control non-derepressible 2
GCN4
general control non-derepressible 4
G3BP1/2
Ras GTPase-activating protein-binding protein 1 and 2
HDAC
histone deacetylases
HRI
heme-regulated inhibitor
hsp
heat shock protein
JNK
c-Jun N-terminal kinase
LLPS
liquid-liquid phase separation
mRNP
messenger ribonucleoprotein
mTOR
mammalian target of rapamycin
NLRP3
NLR Family, Pyrin Domain Containing Protein 3
N protein
nucleocapsid protein
PAI-1
plasminogen activator inhibitor-1
P-body
processing body
PERK
PKR-like endoplasmatic reticulum kinase
PKR
protein kinase RNA-activated
PTM
post-translational modifications
RBP
RNA-binding protein
ROS
reactive oxygen species
SA
sodium arsenite
SG
stress granule
TDP-43
TAR DNA binding protein 43
TIA-1
T cell restricted intracellular antigen-1
TIAR-2
homolog of human TIA-1 inC. elegans pharyngeal muscles
VCP
valosin-containing protein
4E-BP1
eIF4E-binding protein 1
5-FU
5-fluorouracil

Chemical compounds studied in this article

Bortezomib (PubChem CID: 387447)
E)-3-(2,3,4,5-tetrabromophenyl)prop-2-enoic acid (PubChem CID: 16760346)
ISRIB (PubChem CID: 1011240)
Olaparib (PubChem CID: 23725625)
Paclitaxel (PubChem CID: 36314)
PP242 (PubChem CID:135565635)
Psammaplysin F (PubChem CID: 46888580)
Puromycin (PubChem CID: 439530)
Silvestrol (PubChem CID: 11787114)
Sorafenib (PubChem CID: 216239)
Trehalose (PubChem CID: 7427)
5-Fluorouracil (PubChem CID: 3385)

Keywords

eIF2α
G3BP
Microtubule
Post-translational modification
Neurodegenerative disease
Virus infection

Cited by (0)

View Abstract