Abstract
Transthyretin amyloidosis (ATTR amyloidosis) is a fatal systemic disease caused by amyloid deposits of misfolded transthyretin, leading to familial amyloid polyneuropathy and/or cardiomyopathy, or a rare oculoleptomeningeal amyloidosis. A good model system that mimic the disease phenotype is crucial for the development of drugs and treatments for this devastating degenerative disorder. The present models using fruit flies, worms, rodents, non-human primates and induced pluripotent stem cells have helped researchers understand important disease-related mechanisms and test potential therapeutic options. However, the challenge of creating an ideal model still looms, for these models did not recapitulates all symptoms, particularly neurological presentation, of ATTR amyloidosis. Recently, knock-in techniques was used to generate two humanized ATTR mouse models, leading to amyloid deposition in the nerves and neuropathic manifestation in these models. This review gives a recent update on the milestone, progress, and challenges in developing different models for ATTR amyloidosis research.
Highlights
Transthyretin amyloidosis (ATTR) is the most common type of autosomal-dominant hereditary systemic amyloidosis associated with the transthyretin (TTR) protein; with either early- or lateonset presentation in patients (Benson and Kincaid, 2007; Plante-Bordeneuve and Said, 2011; Adams et al, 2012)
ATTR can arise either due to senescent event associated with the wildtype TTR gene leading to wild-type amyloidosis, or hereditary ATTR due to mutations in the TTR gene, leading to either familial amyloid polyneuropathy (ATTR-FAP), familial amyloid cardiomyopathy (ATTR-FAC), or a rare form of oculoleptomeningeal amyloidosis (OLMA) (Ando et al, 2005; Rapezzi et al, 2010; Leung et al, 2013; Mathieu et al, 2018)
A lot of effort is being put into generating successful models for ATTR amyloidosis that can recapitulate all human characteristics of the disease
Summary
Transthyretin amyloidosis (ATTR) is the most common type of autosomal-dominant hereditary systemic amyloidosis associated with the transthyretin (TTR) protein; with either early- or lateonset presentation in patients (Benson and Kincaid, 2007; Plante-Bordeneuve and Said, 2011; Adams et al, 2012). ATTR can arise either due to senescent event associated with the wildtype TTR gene leading to wild-type amyloidosis (formerly known as senile systemic amyloidosis), or hereditary ATTR due to mutations in the TTR gene, leading to either familial amyloid polyneuropathy (ATTR-FAP), familial amyloid cardiomyopathy (ATTR-FAC), or a rare form of oculoleptomeningeal amyloidosis (OLMA) (Ando et al, 2005; Rapezzi et al, 2010; Leung et al, 2013; Mathieu et al, 2018)
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