A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome

Publication: Nature.com | Publication Date: May 4, 2020

Authors: Jana Mahadevan, Shuntaro Morikawa, Takuya Yagi, Damien Abreu, Simin Lu, Kohsuke Kanekura, Cris M. Brown & Fumihiko Urano

Abstract

Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome.

Mahadevan, J., Morikawa, S., Yagi, T. et al. A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome. Lab Invest 100, 1197–1207 (2020). Retrieved February 16, 2024, from https://doi.org/10.1038/s41374-020-0436-1