Publications by authors named "Luke T Nelson"
Article Synopsis
- Mutations in dynamin 2 (DNM2) are linked to two movement disorders: Charcot-Marie-Tooth neuropathies (CMT) and centronuclear myopathy (CNM), primarily affecting the pleckstrin homology domain (PHD).
- CNM mutations disrupt intramolecular interactions that normally inhibit DNM2 activity, while CMT mutations are mostly on a different part of the PHD that is involved in binding phosphoinositides, leading to distinct disease outcomes.
- Research reveals that both DNM2 and CNM-linked mutants create larger, more stable structures in the plasma membrane compared to wild-type DNM2, but CNM mutations appear to have a stronger impact, causing more
Transthyretin (TTR) dissociation is the rate limiting step for both aggregation and subunit exchange. Kinetic stabilisers, small molecules that bind to the native tetrameric structure of TTR, slow TTR dissociation and inhibit aggregation. One such stabiliser is the non-steroidal anti-inflammatory drug (NSAID), diflunisal, which has been repurposed to treat TTR polyneuropathy.
View Article and Find Full Text PDFTransthyretin (TTR) tetramer dissociation is rate limiting for aggregation and subunit exchange. Slowing of TTR tetramer dissociation kinetic stabiliser binding slows cardiomyopathy progression. Quadruplicate subunit exchange comparisons of the drug candidate AG10, and the drugs tolcapone, diflunisal, and tafamidis were carried out at 1, 5, 10, 20 and 30 µM concentrations in 4 distinct pooled wild type TTR (TTRwt) human plasma samples.
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