Neuronal cholesterol synthesis is essential for repair of chronically 
demyelinated lesions in mice

Berghoff, S. A.; Spieth, L.; Sun, T.; Hosang, L.; Depp, C.; Sasmita, A. O.; Vasileva, M. H.; Scholz, P.; Zhao, Y.; Krüger, D.; Wichert, S.; Brown, E. R.; Michail, K.; Nave, K.-A.; Bonn, S.; Odoardi, F.; Rossner, M.; Ischebeck, T.; Edgar, J. M.; Saher, G.

doi:10.1016/j.celrep.2021.109889

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学術論文

Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice

MPS-Authors

/persons/resource/persons202532

Berghoff, S. A.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons213399

Spieth, L.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons270577

Sun, T.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons229789

Depp, C.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons271994

Sasmita, A. O.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons271996

Vasileva, M. H.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182261

Krüger, D.
Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, K.-A.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182137

Edgar, J. M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182386

Saher, G.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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引用

Berghoff, S. A., Spieth, L., Sun, T., Hosang, L., Depp, C., Sasmita, A. O., Vasileva, M. H., Scholz, P., Zhao, Y., Krüger, D., Wichert, S., Brown, E. R., Michail, K., Nave, K.-A., Bonn, S., Odoardi, F., Rossner, M., Ischebeck, T., Edgar, J. M., & Saher, G. (2021). Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice. Cell Reports, 37(4):. doi:10.1016/j.celrep.2021.109889.

引用: https://hdl.handle.net/21.11116/0000-000A-CC75-D

要旨

Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelin-
ating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remye-
lination has to originate from other cellular sources. Here, we show that repair following acute versus chronic
demyelination involves distinct processes. In particular, in chronic myelin disease, when recycling of lipids is
often defective, de novo neuronal cholesterol synthesis is critical for regeneration. By gene expression
profiling, genetic loss-of-function experiments, and comprehensive phenotyping, we provide evidence
that neurons increase cholesterol synthesis in chronic myelin disease models and in patients with multiple
sclerosis (MS). In mouse models, neuronal cholesterol facilitates remyelination specifically by triggering
oligodendrocyte precursor cell proliferation. Our data contribute to the understanding of disease progression
and have implications for therapeutic strategies in patients with MS.