Congrats to Liberty and co-authors on their publication Heat shock protein Grp78/BiP/HspA5 binds directly to TDP-43 and mitigates toxicity associated with disease pathology in Scientific Reports!
Using proximity-dependent biotin identification (BioID), the authors discovered several Hsp70 isoforms that associated with TPD-43. They then showed that HspA5 bound specifically with the RNA-binding domain of TDP-43. They also found that HspA5 was upregulated in a Drosophila model of ALS and in human prefrontal cortex neurons from ALS patient donors. Excitingly, they show that overexpression of HspA5 in the Drosophila ALS model rescued TDP-43-induced toxicity, suggesting that upregulation of HspA5 may have a compensatory role in ALS pathobiology.
