Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Amyloid transthyretin cardiac amyloidosis (ATTR-CA) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction and is an underdiagnosed disorder affecting quality of life and prognosis. This justifies the current search for novel tools for early diagnosis and accurate risk prediction, as well as for safe and effective therapies. In this review we will provide an overview of the main unsolved issues and the most promising research lines on ATTR-CA, ranging from the mechanisms of amyloid formation to therapies.
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http://dx.doi.org/10.23736/S2724-5683.21.05926-3 | DOI Listing |
Minerva Cardiol Angiol
April 2022
Sant'Anna High School, Institute of Life Sciences, Pisa, Italy.
Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Amyloid transthyretin cardiac amyloidosis (ATTR-CA) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction and is an underdiagnosed disorder affecting quality of life and prognosis.
View Article and Find Full Text PDFNucleic Acids Res
December 2016
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Serine and tyrosine site-specific recombinases (SRs and YRs, respectively) provide templates for understanding the chemical mechanisms and conformational dynamics of strand cleavage/exchange between DNA partners. Current evidence suggests a rather intriguing mechanism for serine recombination, in which one half of the cleaved synaptic complex undergoes a 180° rotation relative to the other. The 'small' and 'large' SRs contain a compact amino-terminal catalytic domain, but differ conspicuously in their carboxyl-terminal domains.
View Article and Find Full Text PDFMicrobiol Spectr
August 2015
Department of Biology, University of York, York, United Kingdom.
Nucleic Acids Res
June 2004
Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
The Streptomyces phage phiC31 encodes an integrase belonging to the serine recombinase family of site-specific recombinases. The well studied serine recombinases, the resolvase/invertases, bring two recombination sites together in a synapse, and then catalyse a concerted four-strand staggered break in the DNA substrates whilst forming transient covalent attachments with the recessed 5' ends. Rotation of one pair of half sites by 180 degrees relative to the other pair occurs, to form the recombinant configuration followed by ligation of the DNA backbone.
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