Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis

Abstract

The disease model of familial amyloidotic polyneuropathy—7.2-hMet30 mice—manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21–24 months of age. In addition, non-fibrillar TTR deposits were found in amyloid-negative 7.2hMet30 mice. These results suggested that TTR amyloidogenesis required not only mutant TTR but also an additional factor (or factors) as an etiologic molecule. To determine the differences in serum proteome in amyloid-positive and amyloid-negative mice in the 7.2-hMet30 model, we used proteomic analyses and studied serum samples obtained from these mice. Hemopexin (HPX) and transferrin (Tf) were detected in the serum samples from amyloid-positive mice and were also found in amyloid deposits via immunohistochemistry, but serum samples from amyloid-negative mice did not contain HPX and Tf. These two proteins were also not detected in non-fibrillar TTR deposits. In addition, in silico analyses suggested that HPX and Tf facilitate destabilization of TTR secondary structures and misfolding of TTR. These results suggest that HPX and Tf may be associated with TTR amyloidogenesis after fibrillogenesis in vivo.

Genotype-Phenotype Correlation in WT1 Exon 8 to 9 Missense Variants

“…392-510, including the zinc finger region), which was obtained from PDB (PDB 6B0O chain A). The transferable intermolecular potential with three points (TIP3P) water model 13 and the AMBER03 force field were used for structural optimization of 500-ps molecular dynamics using GROMACS software 14 , as in our previous study 15 . Then, these partial structures were input into APBS software for analysis of the electrostatic surface potential of the DNA binding region, as described previously 16 .…”

Prediction of infectivity of SARS-CoV2: Mathematical model with analysis of docking simulation for spike proteins and angiotensin-converting enzyme 2

“…So, our experimental strategy can achieve high accuracy because we used imitated molecular simulation method for the behavior of biomolecule. In addition, our previous research [29][30][31][32][33][34] suggest the usefulness of this prediction by using our molecular simulation methods.…”

“…Therefore, our experimental strategy achieved high accuracy because we used a molecular simulation method which possibly imitates the behavior of the biomolecules. In addition, our previous research [29][30][31][32][33][34] suggested the value of this prediction that utilized our molecular simulation methods. Additional analyses of binding affinities of other spike proteins of SARS-CoV-2 variants with ACE2 may provide greater accuracy, and such experiments are now in progress.…”

Expression of Amyloidogenic Transthyretin Drives Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease

“…Moreover, recent work demonstrated the ability of TF to physically interact with and prevent the self-assembly and toxicity of b-amyloid peptide oligomers, the amyloidogenic protein species in AD (Giunta et al, 2004;Raditsis et al, 2013). At the same time, recent in vivo data have demonstrated physical interactions between TF and TTR amyloid fibrils (Ohta et al, 2018). Through the use of congophilic fibril formation assays, we demonstrated that iron-free TF at physiologically relevant levels decreased in vitro TTR L55P fibril formation by approximately 60%, implicating TF as a chaperone for hepatic TTRs.…”