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  Defective cholesterol clearance limits remyelination in the aged central nervous system

Cantuti-Castelvetri, L., Fitzner, D., Bosch-Queralt, M., Weil, M.-T., Su, M., Sen, P., et al. (2018). Defective cholesterol clearance limits remyelination in the aged central nervous system. Science, 359(6376), 684-688. doi:10.1126/science.aan4183.

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Cantuti-Castelvetri, Ludovico1, Autor           
Fitzner, Dirk1, Autor           
Bosch-Queralt, Mar2, Autor           
Weil, Marie-Theres1, Autor           
Su, Minhui2, Autor           
Sen, Paromita, Autor
Ruhwedel, Torben3, Autor           
Mitkovski, Miso4, Autor           
Trendelenburg, George, Autor
Lütjohann, Dieter, Autor
Möbius, Wiebke3, Autor           
Simons, Mikael1, Autor           
Affiliations:
1Cellular neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173650              
2Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173648              
3Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173666              
4Light microscopy facility, Wiss. Servicegruppen, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173672              

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 Zusammenfassung: Age-associated decline in regeneration capacity limits the restoration of nervous system functionality after injury. In a model for demyelination, we found that old mice fail to resolve the inflammatory response initiated after myelin damage. Aged phagocytes accumulated excessive amounts of myelin debris, which triggered cholesterol crystal formation and phagolysosomal membrane rupture and stimulated inflammasomes. Myelin debris clearance required cholesterol transporters, including apolipoprotein E. Stimulation of reverse cholesterol transport was sufficient to restore the capacity of old mice to remyelinate lesioned tissue. Thus, cholesterol-rich myelin debris can overwhelm the efflux capacity of phagocytes, resulting in a phase transition of cholesterol into crystals and thereby inducing a maladaptive immune response that impedes tissue regeneration.

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Sprache(n): eng - English
 Datum: 2018-01-042018-02-09
 Publikationsstatus: Erschienen
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1126/science.aan4183
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Titel: Science
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Washington, D.C. : American Association for the Advancement of Science
Seiten: - Band / Heft: 359 (6376) Artikelnummer: - Start- / Endseite: 684 - 688 Identifikator: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1