Open Close
Saelices, L., Pokrzywa, M., Pawelek, K., Eisenberg, D.S. (2018). Assessment of the effects of transthyretin peptide inhibitors in Drosophila models of neuropathic ATTR.  Neurobiol. Disease 120(): 118--125.
FlyBase ID
Publication Type
Research paper

Transthyretin amyloidosis (ATTR) is a fatal disease caused by the systemic aggregation and deposition of transthyretin (TTR), a blood transporter that is mainly produced in the liver. TTR deposits are made of elongated amyloid fibrils that interfere with normal tissue function leading to organ failure. The current standard care for hereditary neuropathic ATTR is liver transplantation or stabilization of the native form of TTR by tafamidis. In our previous work, we explored an additional strategy to halt protein aggregation by capping pre-existing TTR fibrils with structure-based designed peptide inhibitors. Our best peptide inhibitor TabFH2 has shown to be effective at inhibiting not only TTR aggregation but also amyloid seeding driven by fibrils extracted from ATTR patients. Here we evaluate the effects of peptide inhibitors in two Drosophila models of neuropathic ATTR and compared their efficacy with diflunisal, a protein stabilizer currently used off-label for the treatment of ATTR. Our peptide inhibitor TabFH2 was found the most effective treatment, which resulted in motor improvement and the reduction of TTR deposition. Our in vivo study shows that inhibiting TTR deposition by peptide inhibitors may represent a therapeutic strategy for halting the progression of ATTR.

PubMed ID
PubMed Central ID
PMC6186191 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Neurobiol. Disease
    Neurobiology of Disease
    Publication Year
    Data From Reference
    Alleles (3)
    Genes (2)
    Human Disease Models (1)
    Transgenic Constructs (3)