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001 on1164146093;

003 OCoLC;

005 20210129095553.0;

006 m o d ;

007 cr unu||||||||;

008 200709s2020 ncua obm 000 0 eng d;

035 a| (Sirsi) o1164146093;

035 a| (OCoLC)1164146093;

049 a| EREE;

090 a| QP552.C34;

100 1 a| Arreola, Jenette,e| author.?| UNAUTHORIZED;

245 10 a| Transthyretin amyloidosis :b| proteolytic cleavage accelerates G53A TTR misfolding and aggregation /c| by Jenette Arreola.;

246 30 a| Transthyretin amyloidosis proteolytic cleavage accelerates G53A TTR misfolding and aggregation.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2020.;

300 a| 43 pages :b| color illustrations;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 2.485 MB2| rda;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Chemistryc| East Carolina Universityd| 2020.;

500 a| Presented to the faculty of the Department of Chemistry.;

500 a| Advisor: Kwang Hun Lim;

500 a| Title from PDF t.p. (viewed December 2, 2020).;

520 3 a| The proteolytic cleavage of the peptide bond Lys48-Thr49 of the CD loop in TTR pathological mutants S52P and E51_S52dup was previously demonstrated to promote aggregation as a result of tetrameric structure destabilization. Type A and B fibrils were detected in vivo, suggesting alternative TTR misfolding and aggregation mechanisms. The main component of the fibrils was the residue 49-127 fragment. In the proceeding studies, the misfolding and aggregation of G53A TTR, whose mutation is nearby the K48-T49 peptide bond and also associated with TTR amyloidosis, was investigated in thepresence and absence of proteolytic agent, trypsin. Fragmented G53A TTR misfolded and aggregated via a similar mechanism as full-length TTR, but at a faster rate. Similar morphology was exhibited by fragmented and full-length G53A TTR oligomers, as revealed by TEM images, suggesting similar aggregation pathway. G53A TTR in the presence and absence of trypsin generated similar CD and FT-IR profiles, suggesting similar transthyretin morphology during the early and late stages of amyloidosis. Aggregation kinetics was accomplished by monitoring the optical density of G53A TTR in the presence and absence of trypsin and by comparing the ThT fluorescence signal produced. The differences in TTR solubility and ThT enhancement imply G53A TTR aggregation is promoted in the presence of trypsin. Oligomeric effects on mammalian cell line, SH-SY5Y, was probed employing the MTT assay, which determined G53A TTR was more toxic to the cells in the presence of trypsin.;

504 a| Includes bibliographical references.;

650 0 a| Carrier proteins.=| ^A13331;

650 0 a| Amyloidosis.=| ^A906223;

650 0 a| Protein folding.=| ^A312811;

700 1 a| Lim, Kwang Hun,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Chemistry.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/8561;

949 o| wjh;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 5336194;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5336194-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 7/9/2020x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 5336194-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 7/9/2020x| ETDz| HERESOURCE;

Transthyretin amyloidosis : proteolytic cleavage accelerates G53A TTR misfolding and aggregation / by Jenette Arreola.

Author/creator	Arreola, Jenette author.
Other author	Lim, Kwang Hun, degree supervisor.
Other author	East Carolina University. Department of Chemistry.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2020.
Description	43 pages : color illustrations
Supplemental Content	Access via ScholarShip
Subjects	Carrier proteins. Amyloidosis. Protein folding.

Portion of title	Transthyretin amyloidosis proteolytic cleavage accelerates G53A TTR misfolding and aggregation.
Summary	The proteolytic cleavage of the peptide bond Lys48-Thr49 of the CD loop in TTR pathological mutants S52P and E51_S52dup was previously demonstrated to promote aggregation as a result of tetrameric structure destabilization. Type A and B fibrils were detected in vivo, suggesting alternative TTR misfolding and aggregation mechanisms. The main component of the fibrils was the residue 49-127 fragment. In the proceeding studies, the misfolding and aggregation of G53A TTR, whose mutation is nearby the K48-T49 peptide bond and also associated with TTR amyloidosis, was investigated in thepresence and absence of proteolytic agent, trypsin. Fragmented G53A TTR misfolded and aggregated via a similar mechanism as full-length TTR, but at a faster rate. Similar morphology was exhibited by fragmented and full-length G53A TTR oligomers, as revealed by TEM images, suggesting similar aggregation pathway. G53A TTR in the presence and absence of trypsin generated similar CD and FT-IR profiles, suggesting similar transthyretin morphology during the early and late stages of amyloidosis. Aggregation kinetics was accomplished by monitoring the optical density of G53A TTR in the presence and absence of trypsin and by comparing the ThT fluorescence signal produced. The differences in TTR solubility and ThT enhancement imply G53A TTR aggregation is promoted in the presence of trypsin. Oligomeric effects on mammalian cell line, SH-SY5Y, was probed employing the MTT assay, which determined G53A TTR was more toxic to the cells in the presence of trypsin.
General note	Presented to the faculty of the Department of Chemistry.
General note	Advisor: Kwang Hun Lim
General note	Title from PDF t.p. (viewed December 2, 2020).
Dissertation note	Chemistry East Carolina University 2020.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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