We now show that TTR expression in SH-SY5Y human neuroblastoma cells, primary hippocampal neurons and the hippocampus of APP23 mice, is significantly enhanced by heat shock factor 1 (HSF1).
To understand the pathogenic mechanisms of this V30A TTR, we investigated the effects of this mutation on TTR quaternary and tertiary structural stabilities and cytotoxicities against neuroblastoma cells along with the most common variant V30MTTR and the wild-type (WT) TTR.
In complementary tissue culture experiments, recombinant human TTR suppressed the cytotoxicity of soluble Aβ aggregates added to mouse neurons and differentiated human SH-SY5Y neuroblastoma cells.
By probing Cys10SerTTR variants to the human neuroblastoma SH-SY5Y cell line, we have addressed this question, and our results clearly show that formation of an inter-molecular disulphide bridge is not a pre-requisite for TTR cytotoxicity.