TTR (NI-006 Biosimilar) Recombinant Monoclonal Antibody

1. familial amyloid polyneuropathy (FAP) carriers and patients are in an inflammatory state, with the presence of mutated TTR being a trigger of inflammation, especially in FAP carriers. PMID: 28484271
2. In this review, we discussed the role of Ttr in CNS and its possible role in the neuroprotection mechanism of Semax. PMID: 30383932
3. serum prealbumin, and its changes were independent predictors of worse prognosis in acute kidney injury (AKI), and could be potential surrogates to better predict 90-day mortality. PMID: 28145481
4. T139R mutation may expose the buried regions of TTR protein which help in the self association and the increase in the stability may help in the TTR deposition. Structural analysis indicated that F and H strands of TTR are more prone to aggregation. Thus, T139R mutation might cause these residues to be aggregation prone and change in folding rate and validated TTR monomer in diseased cases by Western blot analysis. PMID: 29564986
5. High TTR expression is associated with hypertriglyceridemia. PMID: 29747616
6. Our study characterizes G101S TTR as a stable and N-glycosylable TTR, which may be linked to its non-amyloidogenic characteristic. G101S TTR had slower rate of tetramer dissociation and lower propensity for amyloid fibril formation, especially at mild low pH (4.2 and 4.5), and was likely to have strong hydrophobic interaction among TTR monomers, suggesting relatively higher stability of G101S TTR compared with WT TTR. PMID: 29607936
7. studies of a unique duplication mutation explain its diflunisal-resistant nature, identify misfolding pathways for amyloidogenic TTR variants, and provide therapeutic targets to inhibit amyloid fibril formation by variant TTR. PMID: 29941560
8. At physiological temperature, the monomeric intermediate formed by wild-type TTR under mildly acidic conditions rapidly aggregates into species that are invisible to NMR, leading to loss of the NMR signal at the same rate as the turbidity increase. PMID: 29915031
9. We report here three non-related Hungarian cases of transthyretin familial amyloid polyneuropathy with non-Val30Met mutations (His88Arg in two cases, Phe33Leu in one case) PMID: 29465889
10. A novel amyloidogenic TTR mutation was found in a Dutch family PMID: 28460244
11. Patients with ATTRV30M amyloidosis in non-endemic areas and patients with non-V30M ATTR amyloidosis occurred more frequently than previously believed, and their clinical manifestations were diverse. PMID: 29177547
12. Results indicate that TTR stability is important for its recently described functions in assisting Abeta transport at the BBB and at the liver and also in regulating LRP1 levels and activity. TTR stabilization can serve as an avenue to increase both Abeta elimination and LRP1 levels, which in turn will further participate in Abeta clearance. PMID: 28570028
13. Findings are the first to show that TTR deposition increases disease severity in the murine DMM and aging model of OA. PMID: 28941045
14. This study demonstrated that both cardiac and peripheral vasomotor autonomic dysfunctions were prevalent in late-onset FAP ATTR Val30Met patients from non-endemic areas, even in those without orthostatic intolerance. PMID: 28983659
15. could potentially downregulate the TTR promoter activity; c.200+4A>G might influence the constitutive splicing of TTR mRNA PMID: 27562180
16. Systematic computational prioritization identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. PMID: 27212199
17. This stuidy found two mutations, Thr49Ala(p.Thr69Ala) and Tyr116Ser(p.Tyr136 Ser), were detected in Chinese familial amyloid polyneuropathy patients for the first time. PMID: 27859927
18. The results suggest an association between presumed nonamyloidogenic mutations in the TTR gene and the development of autonomic and small fiber neuropathy. PMID: 28556268
19. Clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity. PMID: 27238058
20. It is one of the major Abeta-binding proteins acting as a neuroprotector in AD. In addition, TTR cleaves Abeta peptide in vitro. PMID: 28780366
21. Stroke patients with lower transthyretin levels had poorer Functional Independence Measure outcomes and tended not to be discharged to their own homes. PMID: 28314625
22. TTR expression varied across human populations PMID: 28335735
23. Cell-based experiments showed that overexpression of TTR could improve HK-2 cell viability and inhibit apoptosis. PMID: 29040977
24. These results clarify a negligible degree of unfolding of beta-strand C in the formation of the amyloidogenic state and establish the concept that TTR is a highly plastic protein able to populate at least three distinct conformational states. PMID: 28478513
25. A strong phenotypic heterogeneity was demonstrated across coding mutations causing TTR amyloidosis. Non-coding variants affect TTR expression and, consequently, phenotypic presentation in carriers of amyloidogenic mutations. PMID: 28635949
26. Serum prealbumin was significantly lower in patients with versus those without post-stroke depression, and was a significant predictor of post-stroke depression after adjusting for confounding risk factors. PMID: 27693925
27. TTR induced apoptosis of retinal microvascular endothelial cells in an environment that simulated hypoxia. PMID: 28950253
28. Data suggest that transthyretin exhibits site-specific solvation of the indole ring of tryptophans W41 and W79; these studies involved incorporation of tryptophan labeled with fluorine at 5 or 6 positions (5-fluorotryptophan/5FW or 6-fluorotryptophan/6FW) into recombinant TTR; replacement of fluorine at 5-position of a tryptophan with one at adjacent 6-position emphasizes delicate balance of stability in TTR tetramer. PMID: 28920433
29. This study shows that highly destabilized, aggregation-prone TTR variants are secreted as both native tetramers and non-native conformations that accumulate as high-molecular-weight oligomers. PMID: 27720586
30. The role of transthyretin in normal pregnancy is reviewed. PMID: 27650990
31. the role of H88 and the hydrogen bond network in the stability of TTR PMID: 28563699
32. we identify a somatic mosaicism, in several subjects affected by familial amyloidotic polyneuropathy, involving the dominant c.325G>C mutation of the TTR gene PMID: 28508289
33. The role of Transthyretin in the regulation of Ubc9 SUMOylation PMID: 27501389
34. Gene sequencing revealed a phenylalanine-->isoleucine mutation in the 33rd position of exon 2 of TTR in 1 patient of 1 pedigree, confirming the diagnosis of FAP. Two patients subsequently were found to have sensorimotor autonomic neuropathy, whereas 2 others had subclinical autonomic dysfunction. PMID: 28412068
35. TTR V30M aggregates and autophagy impairment are associated with Transthyretin amyloidoses . PMID: 27382986
36. In Afro-Caribbean patients living in London, ATTR V122I is an underappreciated cause of heart failure, and cardiomyopathy is often misattributed to hypertension. PMID: 27618855
37. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. PMID: 27386769
38. In the bound state, the Hsp90 dimer predominantly populates an open conformation, and transthyretin retains its globular structure. PMID: 28218749
39. findings show that, at physiologically-relevant protein concentrations, the refolding pathways of WT-TTR and amyloidogenic variant V30M-TTR follow a common mechanism observed among other tetrameric proteins; although sharing the same kinetic mechanism, V30M-TTR refolds at a slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways PMID: 27589730
40. This study reports the discovery of a TTR mutant, N98A, that was more effective at inhibiting ABETA aggregation than wild-type (WT) TTR, although N98A and WT bound ABETA equally. PMID: 27099354
41. Results provide evidence that TTR acts as a carrier of Abeta at the blood-brain-barrier and liver, using LRP1. PMID: 26837706
42. The study reports a Japanese family with hereditary ATTR amyloidosis with the TTR G47R mutation in which one family member developed the disease at the age of 13. PMID: 27206384
43. a point mutation was identified in the upstream regulatory region of the TTR gene in a Han Chinese family with familial vitreous amyloidosis. PMID: 27051017
44. Data indicte that the use of polyethylene glycol (PEG) to crystallize transthyretin (TTR complexes have resulted in a new trigonal polymorph with two tetramers in the asymmetric unit. PMID: 26796656
45. A novel autosomally inherited Lys90Glu mutation in the TTR gene in a family with vitreous amyloidosis and carpal tunnel syndrome. PMID: 26828956
46. illustrates the diversity of symptoms encountered in homozygote ATTR V30M patients PMID: 26587769
47. Caucasian patients with the Val142Ile pathogenic variant have phenotypic manifestations similar to African-Americans PMID: 26428663
48. Data suggest that well-structured AB loop regions of TTR in native/homotetrameric/stable state become dissociated/disordered/unfolded at low pH; during refolding, structural perturbations in AB loop appear and facilitate misfolding and amyloid formation. PMID: 26998642
49. Eight water molecules stabilize the dimeric structure through an extensive hydrogen-bonding network. PMID: 26527142
50. Study elucidated alterations in TTR, APP and the global gene expression profile in the frontal cortex between idiopathic normal pressure hydrocephalus patients and nondemented control brain PMID: 26444765

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HGNC: 12405

OMIM: 105210

KEGG: hsa:7276

STRING: 9606.ENSP00000237014

UniGene: Hs.427202