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.
| Original language | English |
|---|---|
| Pages (from-to) | 394-409 |
| Number of pages | 16 |
| Journal | Trends in Molecular Medicine |
| Volume | 27 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2021 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020 Elsevier Ltd
Funding
We would like to acknowledge all the extensive work in this field that, owing to space constraints, we are unable to cite. A.G. has a financial interest in Goldfinch Biopharma which was reviewed and is managed by Brigham and Women's Hospital and Partner's Healthcare and by the Broad Institute of MIT and Harvard in accordance with their conflict of interest policies.
| Funders | Funder number |
|---|---|
| Harvard University | |
| Broad Institute |
Keywords
- MUC1 kidney disease
- P24
- TMED
- autosomal dominant tubulointerstitial kidney disease (ADTKD)
- cargo quality control
- chronic kidney disease
- proteinopathies
- rare diseases