title: Peroxisomes in brain development and function.
abstract: Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer's disease, autism and amyotrophic lateral sclerosis.
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: johannes.berger@meduniwien.ac.at.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: fabian.dorninger@meduniwien.ac.at.
authors.forename: Fabian
authors.initials: F
authors.lastname: Dorninger
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: sonja.forss-petter@meduniwien.ac.at.
authors.forename: Sonja
authors.initials: S
authors.lastname: Forss-Petter
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: markus.kunze@meduniwien.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Kunze
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D009154:Mutation; D018901:Peroxisomal Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020675:Peroxisomes / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D009435:Synaptic Transmission
chemical_list: D008565:Membrane Proteins; D020033:Protein Isoforms; D000074183:ATPases Associated with Diverse Cellular Activities; C111808:PEX1 protein, human
keywords: D-bifunctional protein deficiency; Lipid metabolism; Plasmalogen; Rhizomelic chondrodysplasia punctata; X-linked adrenoleukodystrophy; Zellweger spectrum disorder