A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome.

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.

• Authors: Jana Mahadevan, Shuntaro Morikawa, Takuya Yagi, Damien Abreu, Simin Lu, Kohsuke Kanekura, Cris M Brown, Fumihiko Urano
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 100 Issue 9 Pg. 1197-1207 (09 2020) ISSN: 1530-0307 [Electronic] United States
• PMID: 32366942 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MANF protein, mouse
• Nerve Growth Factors

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cells, Cultured
• Endoplasmic Reticulum (metabolism)
• Endoplasmic Reticulum Stress (drug effects)
• Humans
• Insulin-Secreting Cells (cytology, drug effects, metabolism)
• Mice, Transgenic
• Nerve Growth Factors (pharmacology)
• Rats
• Wolfram Syndrome (metabolism, physiopathology, prevention & control)