Relationships between Stress Granules, Oxidative Stress, and Neurodegenerative Diseases

Figure 1

Schematic diagram of normal stress granule (SG) formation and the transition from normal SGs to pathological SGs. During transient oxidative stress such as ROS, translation of mRNA is stalled, and the nuclear exported nontranslating mRNPs (mRNA and many translation initiation factors such as eIF4G/E, Pab1, and Pbp1) form normal SGs in the cytoplasm through sequestration of RNA-binding proteins like primary nucleators (G3BP1/2, TIA-1, and TIAR). These SGs are reversible and dynamic, and they exchange components with the cytoplasm. Severe stress or mutations that decrease SG clearance or that enhance amyloid-like aggregation or can cause normal SGs to become pathological, irreversible SGs. Moreover, mutations in many RNA-binding proteins (TDP-43, FUS, ataxin-2, HuR, etc.) and non-RNA-binding proteins (tau, C9ORF72, etc.) can accelerate this transition via their self-aggregation (oligomerization), which is promoted by persistent oxidative stress or aging.