Transthyretin mutagenesis: impact on amyloidogenesis and disease.
Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are...
| Publicado en: | Critical Reviews in Clinical Laboratory Sciences Vol. 61; no. 7; pp. 616 - 641 |
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| Autores principales: | , , |
| Formato: | pictorial review tables/charts Journal Article |
| Publicado: |
Taylor & Francis Ltd
Nov2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=180554433&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 180554433 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10408363 1AV jtl: Critical Reviews in Clinical Laboratory Sciences issn: 10408363 maglogo: Y pubinfo: dt: Nov2024 vid: 61 iid: 7 pid: 377 pub: Taylor & Francis Ltd place: Philadelphia, Pennsylvania artinfo: ui: 180554433 177769662 180554433 180554433 10.1080/10408363.2024.2350379 180554433 ppf: 616 ppct: 25 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Transthyretin mutagenesis: impact on amyloidogenesis and disease. aug: au: Almeida, Zaida L. Vaz, Daniela C. Brito, Rui M. M. affil: Chemistry Department and Coimbra Chemistry Centre - Institute of Molecular Sciences (CQC-IMS), University of Coimbra, Coimbra, Portugal sug: subj: Amyloidosis Familial and Genetic Proteins Metabolism Amino Acids Metabolism Mutation Myocardial Diseases Carpal Tunnel Syndrome Arachnoid Cysts Aspartic Acid Tryptophan Amyloidosis Symptoms Serum Albumin Metabolism Cell Death ab: Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are hallmarks of ATTRwt and ATTRv amyloidosis, respectively. The formation of soluble amyloid aggregates and the accumulation of insoluble amyloid fibrils and deposits in multiple tissues can lead to organ dysfunction and cell death. The most frequent manifestations of ATTR are polyneuropathies and cardiomyopathies. However, clinical manifestations such as carpal tunnel syndrome, leptomeningeal, and ocular amyloidosis, among several others may also occur. This review provides an up-to-date listing of all single amino-acid mutations in TTR known to date. Of approximately 220 single-point mutations, 93% are considered pathogenic. Aspartic acid is the residue mutated with the highest frequency, whereas tryptophan is highly conserved. "Hot spot" mutation regions are mainly assigned to β-strands B, C, and D. This manuscript also reviews the protein aggregation models that have been proposed for TTR amyloid fibril formation and the transient conformational states that convert native TTR into aggregation-prone molecular species. Finally, it compiles the various in vitro TTR aggregation protocols currently in use for research and drug development purposes. In short, this article reviews and discusses TTR mutagenesis and amyloidogenesis, and their implications in disease onset. pubtype: Academic Journal doctype: pictorial review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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