Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis.
Nat Chem Biol
; 9(2): 126-33, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23292650
ABSTRACT
Liver X receptors (Lxrα and Lxrß) 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.
Full text:
1
Database:
MEDLINE
Main subject:
Mesencephalon
/
Neurogenesis
/
Orphan Nuclear Receptors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2013
Type:
Article
Affiliation country:
Sweden