Abstract：
:Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (24,25-EC) was found to be the most potent and abundant Lxr ligand in the developing mouse midbrain. Both Lxr ligands promoted neural development in an Lxr-dependent manner in zebrafish in vivo. Notably, each ligand selectively regulated the development of distinct midbrain neuronal populations. Whereas cholic acid increased survival and neurogenesis of Brn3a-positive red nucleus neurons, 24,25-EC promoted dopaminergic neurogenesis. These results identify an entirely new class of highly selective and cell type-specific regulators of neurogenesis and neuronal survival. Moreover, 24,25-EC promoted dopaminergic differentiation of embryonic stem cells, suggesting that Lxr ligands may thus contribute to the development of cell replacement and regenerative therapies for Parkinson's disease.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Theofilopoulos S,Wang Y,Kitambi SS,Sacchetti P,Sousa KM,Bodin K,Kirk J,Saltó C,Gustafsson M,Toledo EM,Karu K,Gustafsson JÅ,Steffensen KR,Ernfors P,Sjövall J,Griffiths WJ,Arenas Edoi
10.1038/nchembio.1156subject
Has Abstractpub_date
2013-02-01 00:00:00pages
126-33issue
2eissn
1552-4450issn
1552-4469pii
nchembio.1156journal_volume
9pub_type
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