A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome
| Autor: | Takuya Yagi, Cris M. Brown, Simin Lu, Fumihiko Urano, Jana Mahadevan, Damien Abreu, Kohsuke Kanekura, Shuntaro Morikawa |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Retinal degeneration Programmed cell death Wolfram syndrome Genetic enhancement Apoptosis Mice Transgenic Endoplasmic Reticulum Article Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Neurotrophic factors Cell Line Tumor Insulin-Secreting Cells medicine Animals Humans Nerve Growth Factors Molecular Biology Cells Cultured Cell Proliferation business.industry Cell growth Endoplasmic reticulum Neurodegeneration Type 2 diabetes Wolfram Syndrome Cell Biology Endoplasmic Reticulum Stress medicine.disease Rats 030104 developmental biology Cancer research business 030217 neurology & neurosurgery |
| Zdroj: | Laboratory Investigation; a Journal of Technical Methods and Pathology |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/s41374-020-0436-1 |
| Popis: | 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. Wolfram syndrome is a prototype of endoplasmic reticulum (ER) stress disorder characterized by diabetes, visual impairment, and neurodegeneration. Currently, there is no treatment that can halt or reverse the disease progression. Here, the authors show that mesencephalic astrocyte-derived neurotrophic factor-based regenerative gene therapy is an emerging therapeutic strategy for Wolfram syndrome and other ER stress-related disorders. |
| Databáze: | OpenAIRE |
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