Small Heat Shock Proteins Collaborate with FAIM to Prevent Accumulation of Misfolded Protein Aggregates

Cells and tissues are continuously subject to environmental insults, such as heat shock and oxidative stress, which cause the accumulation of cytotoxic, aggregated proteins. We previously found that Fas Apoptosis Inhibitory Molecule (FAIM) protects cells from stress-induced cell death by preventing abnormal generation of protein aggregates similar to the effect of small heat shock proteins (HSPs). Protein aggregates are often associated with neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we sought to determine how FAIM protein dynamics change during cellular stress and how FAIM prevents the formation of amyloid-beta aggregates/fibrils, one of the pathological hallmarks of AD. Here, we found that the majority of FAIM protein shifts to the detergent-insoluble fraction in response to cellular stress. A similar shift to the insoluble fraction was also observed in small heat shock protein (sHSP) family molecules, such as HSP27, after stress. We further demonstrate that FAIM is recruited to sHSP-containing complexes after cellular stress induction. These data suggest that FAIM might prevent protein aggregation in concert with sHSPs. In fact, we observed the additional effect of FAIM and HSP27 on the prevention of protein aggregates using an in vitro amyloid-beta aggregation model system. Our work provides new insights into the interrelationships among FAIM, sHSPs, and amyloid-beta aggregation.

Automated summary

This study found that Fas Apoptosis Inhibitory Molecule (FAIM) can prevent protein aggregation during cellular stress, especially the aggregation of amyloid-beta protein, a pathological hallmark of Alzheimer's disease. The study also revealed the role of FAIM in preventing protein aggregation in conjunction with small heat shock proteins (sHSPs). These findings provide new insights into the interrelationships among FAIM, sHSPs, and amyloid-beta aggregation.