CDNF and MANF regulate ER stress in a tissue-specific manner.

Abstract

Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) display cytoprotective effects in animal models of neurodegenerative diseases. These endoplasmic reticulum (ER)-resident proteins belong to the same protein family and function as ER stress regulators. The relationship between CDNF and MANF function, as well as their capability for functional compensation, is unknown. We aimed to investigate these questions by generating mice lacking both CDNF and MANF. Results showed that CDNF-deficient Manf-/- mice presented the same phenotypes of growth defect and diabetes as Manf-/- mice. In the muscle, CDNF deficiency resulted in increased activation of unfolded protein response (UPR), which was aggravated when MANF was ablated. In the brain, the combined loss of CDNF and MANF did not exacerbate UPR activation caused by the loss of MANF alone. Consequently, CDNF and MANF deficiency in the brain did not cause degeneration of dopamine neurons. In conclusion, CDNF and MANF present functional redundancy in the muscle, but not in the other tissues examined here. Thus, they regulate the UPR in a tissue-specific manner.

• Authors: Emmi Pakarinen, Päivi Lindholm, Mart Saarma, Maria Lindahl
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 79 Issue 2 Pg. 124 (Feb 07 2022) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 35129674 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• MANF protein, mouse
• Nerve Growth Factors
• cdnf protein, mouse

Topics

• Animals
• Dopaminergic Neurons (metabolism, pathology)
• Endoplasmic Reticulum (metabolism)
• Endoplasmic Reticulum Stress
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nerve Growth Factors (metabolism)
• Neurodegenerative Diseases (metabolism)
• Unfolded Protein Response