title: Central nervous system pathology in MFP2 deficiency: insights from general and conditional knockout mouse models.
abstract: Multifunctional protein-2 (MFP2), also known as D-bifunctional protein, is a central enzyme of the peroxisomal β-oxidation pathway. Defects in this enzyme are associated with a spectrum of neurological disorders encompassing developmental and degenerative pathologies. In order to investigate the cellular and molecular mechanisms of these neuropathologies, mouse models with general and cell type selective loss of MFP2 were generated. In this review the distinct anomalies in the CNS of adult Mfp2 knockout mice are discussed, in particular the cerebellar degeneration and neuroinflammation. The potential underlying mechanisms are considered with regard to the cellular origin and biochemical causes. Finally, the similarities and differences between the CNS phenotypes of mice lacking MFP2 and mice with peroxisome biogenesis disorders are assessed.
authors: Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven B-3000, Belgium. Electronic address: Simon.Verheijden@pharm.kuleuven.be.
authors: Simon
authors: S
authors: Verheijden
authors: Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven B-3000, Belgium. Electronic address: Lien.Beckers@pharm.kuleuven.be.
authors: Lien
authors: L
authors: Beckers
authors: Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven B-3000, Belgium. Electronic address: Stephanie.Demunter@pharm.kuleuven.be.
authors: Stephanie
authors: S
authors: De Munter
authors: LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Leuven B-3000, Belgium. Electronic address: Paul.Vanveldhoven@med.kuleuven.be.
authors: Paul P
authors: PP
authors: Van Veldhoven
authors: Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven B-3000, Belgium. Electronic address: Myriam.Baes@pharm.kuleuven.be.
authors: Myriam
authors: M
authors: Baes
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018901:Peroxisomal Disorders / Q000473:pathology; D064029:Peroxisomal Multifunctional Protein-2 / Q000172:deficiency*
chemical_list: C491288:Hsd17b4 protein, mouse; D064029:Peroxisomal Multifunctional Protein-2
keywords: Cerebellum; Multifunctional protein-2; Neuroinflammation; Peroxisomes; Purkinje cell; β-Oxidation