% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Berghoff:155681,
      author       = {Berghoff, Stefan A and Spieth, Lena and Sun, Ting and
                      Hosang, Leon and Schlaphoff, Lennart and Depp, Constanze and
                      Düking, Tim and Winchenbach, Jan and Neuber, Jonathan and
                      Ewers, David and Scholz, Patricia and van der Meer,
                      Franziska and Cantuti-Castelvetri, Ludovico and Sasmita,
                      Andrew O and Meschkat, Martin and Ruhwedel, Torben and
                      Möbius, Wiebke and Sankowski, Roman and Prinz, Marco and
                      Huitinga, Inge and Sereda, Michael W and Odoardi, Francesca
                      and Ischebeck, Till and Simons, Mikael and
                      Stadelmann-Nessler, Christine and Edgar, Julia M and Nave,
                      Klaus-Armin and Saher, Gesine},
      title        = {{M}icroglia facilitate repair of demyelinated lesions via
                      post-squalene sterol synthesis.},
      journal      = {Nature neuroscience},
      volume       = {24},
      number       = {1},
      issn         = {1546-1726},
      address      = {New York, NY},
      publisher    = {Nature America},
      reportid     = {DZNE-2021-00849},
      pages        = {47 - 60},
      year         = {2021},
      abstract     = {The repair of inflamed, demyelinated lesions as in multiple
                      sclerosis (MS) necessitates the clearance of
                      cholesterol-rich myelin debris by microglia/macrophages and
                      the switch from a pro-inflammatory to an anti-inflammatory
                      lesion environment. Subsequently, oligodendrocytes increase
                      cholesterol levels as a prerequisite for synthesizing new
                      myelin membranes. We hypothesized that lesion resolution is
                      regulated by the fate of cholesterol from damaged myelin and
                      oligodendroglial sterol synthesis. By integrating gene
                      expression profiling, genetics and comprehensive
                      phenotyping, we found that, paradoxically, sterol synthesis
                      in myelin-phagocytosing microglia/macrophages determines the
                      repair of acutely demyelinated lesions. Rather than
                      producing cholesterol, microglia/macrophages synthesized
                      desmosterol, the immediate cholesterol precursor.
                      Desmosterol activated liver X receptor (LXR) signaling to
                      resolve inflammation, creating a permissive environment for
                      oligodendrocyte differentiation. Moreover, LXR target gene
                      products facilitated the efflux of lipid and cholesterol
                      from lipid-laden microglia/macrophages to support
                      remyelination by oligodendrocytes. Consequently,
                      pharmacological stimulation of sterol synthesis boosted the
                      repair of demyelinated lesions, suggesting novel therapeutic
                      strategies for myelin repair in MS.},
      keywords     = {Animals / Cholesterol: metabolism / Demyelinating Diseases:
                      pathology / Desmosterol: metabolism / Encephalomyelitis,
                      Autoimmune, Experimental / Female / Gene Expression
                      Profiling / Humans / Inflammation: metabolism /
                      Inflammation: pathology / Lipid Metabolism / Liver X
                      Receptors: metabolism / Mice / Mice, Inbred C57BL /
                      Microglia: physiology / Middle Aged / Multiple Sclerosis /
                      Oligodendroglia: metabolism / Phagocytosis / Squalene:
                      metabolism / Sterols: biosynthesis / Liver X Receptors (NLM
                      Chemicals) / Nr1h3 protein, mouse (NLM Chemicals) / Sterols
                      (NLM Chemicals) / Desmosterol (NLM Chemicals) / Squalene
                      (NLM Chemicals) / Cholesterol (NLM Chemicals)},
      cin          = {AG Simons},
      ddc          = {610},
      cid          = {I:(DE-2719)1110008},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33349711},
      pmc          = {pmc:PMC7116742},
      doi          = {10.1038/s41593-020-00757-6},
      url          = {https://pub.dzne.de/record/155681},
}