tretinoin and Amyloid-Neuropathies--Familial

Familial transthyretin amyloidosis (ATTR) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe detailed methodologies for the directed differentiation of protein folding disease-specific iPSCs into hepatocytes that produce mutant protein, and neural-lineage cells often targeted in disease. Methodologies are also described for the construction of multisystem models and drug screening using iPSCs.

Topics: Activins; Amyloid Neuropathies, Familial; Brain-Derived Neurotrophic Factor; Cell Culture Techniques; Cell Differentiation; Cell Survival; Cellular Reprogramming; Collagen; Drug Combinations; Gene Expression; Glial Cell Line-Derived Neurotrophic Factor; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Laminin; Models, Biological; Mutation; Neurons; Primary Cell Culture; Protein Folding; Proteoglycans; Receptors, Albumin; Tretinoin; Wnt3 Protein