A Rare Kidney Disease To Cure Them All? Towards Mechanism-Based Therapies for Proteinopathies.

A Rare Kidney Disease To Cure Them All? Towards Mechanism-Based Therapies for Proteinopathies. Trends Mol Med. 2020 Dec 16;: Authors: Dvela-Levitt M, Shaw JL, Greka A Abstract Autosomal dominant tubulointerstitial kidney diseases (ADTKDs) are a group of rare genetic diseases that lead to kidney failure. Mutations in the MUC1 gene cause ADTKD-MUC1 (MUC1 kidney disease, MKD), a disorder with no available therapies. Recent studies have identified the molecular and cellular mechanisms that drive MKD disease pathogenesis. Armed with patient-derived cell lines and pluripotent stem cell (iPSC)-derived kidney organoids, it was found that MKD is a toxic proteinopathy caused by the intracellular accumulation of misfolded MUC1 protein in the early secretory pathway. We discuss the advantages of studying rare monogenic kidney diseases, describe effective patient-derived model systems, and highlight recent mechanistic insights into protein quality control that have implications for additional proteinopathies beyond rare kidney diseases. PMID: 33341352 [PubMed - as supplied by publisher]
Source: Trends in Molecular Medicine - Category: Molecular Biology Authors: Tags: Trends Mol Med Source Type: research