Targeting stress granules: A novel therapeutic strategy for human diseases

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.

Keywords: 5-Fluorouracil (PubChem CID: 3385); Bortezomib (PubChem CID: 387447); E)-3-(2,3,4,5-tetrabromophenyl)prop-2-enoic acid (PubChem CID: 16760346); G3BP; ISRIB (PubChem CID: 1011240); Microtubule; Neurodegenerative disease; Olaparib (PubChem CID: 23725625); PP242 (PubChem CID:135565635); Paclitaxel (PubChem CID: 36314); Post-translational modification; Psammaplysin F (PubChem CID: 46888580); Puromycin (PubChem CID: 439530); Silvestrol (PubChem CID: 11787114); Sorafenib (PubChem CID: 216239); Trehalose (PubChem CID: 7427); Virus infection; eIF2α.