A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome

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

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish
JournalLaboratory Investigation
DOIs
StateAccepted/In press - Jan 1 2020

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    Mahadevan, J., Morikawa, S., Yagi, T., Abreu, D., Lu, S., Kanekura, K., Brown, C. M., & Urano, F. (Accepted/In press). A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome. Laboratory Investigation. https://doi.org/10.1038/s41374-020-0436-1