Neuroprotective effect against amyloidogenic transthyretin aggregates - Induced cytotoxicity on human neuroblastoma cell by phenolic-rich extract.

Transthyretin (ATTR) amyloidosis is a progressive and life-threatening neurodegenerative disease caused by aggregation of the plasma transport protein, transthyretin, for which treatment is rare and cure unavailable. is a small edible herb with a long history of neurological application in ethnomedicine. This work investigated whether hydrophilic extract of (CAB) could suppress the toxic effects of transthyretin amyloid aggregate (TTRa) in cell model derived from the same target.

Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of (L.) Wettst (Brahmi) Extract.

The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative.

The catalytic kinetics of chicken transthyretin towards human Aβ.

The novel property of transthyretin (TTR) as a protease has been proposed to be significant. However, the study of TTR proteolysis properties has not been completely elucidated. Herein, we first report the catalytic activity of chicken TTR from plasma determined by using fluorescently labeled amyloid beta 1-42 peptide (Aβ), and compared it with human TTR (human TTR) from plasma and recombinant Crocodylus porosus TTR.

The hydrophobic C-terminal sequence of transthyretin affects its catalytic kinetics towards amidated neuropeptide Y.

Transthyretin (TTR) is a transporter for thyroid hormone and retinol binding protein that has recently been reported to have proteolytic activity against certain substrates, including amidated neuropeptide Y (NPY). However, the proteolytic activity of TTR towards NPY is not fully understood. Here, we used fluorescence-based assays to determine the catalytic kinetics of human TTR towards human amidated NPY.

Structural Stabilization of Human Transthyretin by (L.) Urban Extract: Implications for TTR Amyloidosis.

Transthyretin is responsible for a series of highly progressive, degenerative, debilitating, and incurable protein misfolding disorders known as transthyretin (TTR) amyloidosis. Since dissociation of the homotetrameric protein to its monomers is crucial in its amyloidogenesis, stabilizing the native tetramer from dissociating using small-molecule ligands has proven a viable therapeutic strategy. The objective of this study was to determine the potential role of the medicinal herb on human transthyretin (huTTR) amyloidogenesis.

Increasing the length and hydrophobicity of the C-terminal sequence of transthyretin strengthens its binding affinity to retinol binding protein.

Transthyretin (TTR) is a transporter for thyroid hormone (TH) and retinol, the latter via binding with retinol binding protein (RBP). Both the N-terminal and C-terminal regions of the TTR subunit are located in close proximity to the central binding channel for ligands. During the evolution of vertebrates, these regions changed in length and hydropathy.

Gene structure and evolution of transthyretin in the order Chiroptera.

Bats are mammals in the order Chiroptera. Although many extensive morphologic and molecular genetics analyses have been attempted, phylogenetic relationships of bats has not been completely resolved. The paraphyly of microbats is of particular controversy that needs to be confirmed.

Effect of the N-terminal sequence on the binding affinity of transthyretin for human retinol-binding protein.

During vertebrate evolution, the N-terminal region of transthyretin (TTR) subunit has undergone a change in both length and hydropathy. This was previously shown to change the binding affinity for thyroid hormones (THs). However, it was not known whether this change affects other functions of TTR.

In vitro thyroid hormone-disrupting activity in effluents and surface waters in Thailand.

The thyroid hormone (TH)-disrupting activity of effluents and environmental water samples in Thailand was surveyed by three in vitro bioassays with different endpoints. These assays test the potency of competitive binding with the active form of TH, 3,3',5-[(125)I]triiodo-l-thyronine (T(3)), to the plasma transport protein transthyretin (TTR) and TH receptor (TR; the TTR assay and TR assay, respectively) and the interference with the cellular T(3)-signaling pathway through TR-mediated luciferase gene activation (the luc assay). The TH-disrupting activity in water samples collected from paper manufacturing plants (PMPs), the canal Khlong U-Taphao, and a sewage-treatment plant (STP) was detected predominantly in the dichloromethane/methanol or methanol fractions of solid-phase extraction, suggesting a similar hydrophobic nature of the causative contaminants.

Change in structure of the N-terminal region of transthyretin produces change in affinity of transthyretin to T4 and T3.

The relationship between the structure of the N-terminal sequence of transthyretin (TTR) and the binding of thyroid hormone was studied. A recombinant human TTR and two derivatives of Crocodylus porosus TTRs, one with the N-terminal sequence replaced by that of human TTR (human/crocTTR), the other with the N-terminal segment removed (truncated crocTTR), were synthesized in Pichia pastoris. Subunit mass, native molecular weight, tetramer formation, cross-reactivity to TTR antibodies and binding to retinol-binding protein of these recombinant TTRs were similar to TTRs found in nature.

Crocodile transthyretin: structure, function, and evolution.

Structure and function were studied for Crocodylus porosus transthyretin (crocTTR), an important intermediate in TTR evolution. The cDNA for crocTTR mRNA was cloned and sequenced and the amino acid sequence of crocTTR was deduced. In contrast to mammalian TTRs, but similar to avian and lizard TTRs, the subunit of crocTTR had a long and hydrophobic NH(2)-terminal region.