Irina Ritsch furthers understanding of protein aggregation in cardiac amyloidosis

PNAS, the journal of the US National Academy of Sciences, has published a paper co-authored by Branco Weiss Fellow Irina Ritsch. In their proof-of-principle article, the authors establish a new kind of assay to understand the misfolding of transthyretin (TTR), a blood plasma hormone carrier protein, under turbulent flow conditions. Misfolding and aggregation of the protein leads to TTR amyloidosis, which plays a causative role in age-related and familial neurodegenerative and cardiac diseases. Deposition of wild type (WT) TTR fibrils in the heart occurs in up to 25% of the elderly, yet the molecular mechanism of aggregation under physiological conditions remains elusive.

The new methodology, highlighted already in a commentary article by Sheena Radford and colleagues in PNAS, allowed the researchers to study protein aggregation after application of turbulent flow conditions through the lens of structural biology. In the case of TTR they achieved a novel understanding of the destabilization of TTR at the native oligomerization interfaces. The findings are the first of their kind for wild-type TTR aggregation at neutral pH and enable future efforts to find mechanisms to prevent harmful TTR aggregation linked to transthyretin amyloidosis in patients.

Read the paper on the PNAS website

Read a favorable comment by Sheena Radford and colleagues in PNAS