In most peroxisomal disorders the nervous system is severely affected which explains the clinical and community burden they represent. This is the first book to focus not only on the mutations causing these inherited illnesses, but also on mechanisms that regulate, suppress or enhance expression of genes and their products (enzymes). Indeed since the success and completion of the Human Genome Project all genes (coding DNA sequences) are known. However, of many, their function, and the role of the gene product has not been determined. An example is X-linked adrenoleukodystrophy, the most frequent peroxisomal disorder. Children are born healthy, but in more than 1 out of 3, demyelination of the brain starts unpredictably and they die in a vegetative state. The gene mutated in most families has been known for 10 years; but the true role of the encoded protein, ALDp, is still speculative; and within the same family, very severe and asymptomatic clinical histories co-exist, unexplained by the mutation.
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ISBN-13
978-1-4419-9072-3 (9781441990723)
DOI
10.1007/978-1-4419-9072-3
Schweitzer Klassifikation
Why study regulation of genes in inherited disorders?.- Variable Expression Of Peroxisomes And Their Disorders.- Phenotypic variability (heterogeneity) of peroxisomal disorders.- Mulibrey nanism: a novel peroxisomal disorder.- Peroxisomes during development and in distinct cell types.- Tissue-specific expression of two peroxisomal 3-ketoacyl-CoA thiolase genes in wild and PPAR?-null mice and
induction by fenofibrate.- Clinical features and retinal function in patients with adult Refsum syndrome.- Is there a phenotype/genotype correlation in peroxisome biogenesis disorders (PBDs)?.- Biochemical markers predicting survival in peroxisome biogenesis disorders.- Identification of PEX7 as the second gene involved in Refsum disease.- Genetic heterogeneity in Japanese patients with peroxisome biogenesis disorders and evidence for a founder haplotype for the most common mutation in PEXI0 gene.- Disturbances of valine metabolism in patients with peroxisomal biogenesis disorders.- Mouse models and genetic modifiers in X-linked adrenoleukodystrophy.- Evidence against the adrenoleukodystrophy-related gene acting as a modifier of X-adrenoleukodystrophy.- Peroxisome mosaics.- Resolution of the molecular defect in a patient with peroxisomal mosaicism in the liver.- Lessons from knockout mice I: Phenotypes of mice with peroxisome biogenesis disorders.- Lessons from knockout mice II: Mouse models for peroxisomal disorders with single protein deficiency.- Molecular Mechanisms Of Gene Regulation.- DNA methylation and human diseases.- RNA silencing.- Imprinting.- Histone Modifications-Marks for Gene Expression?.- A paradigm for gene regulation: inflammation, NF-KB and PPAR.- Investigative Techniques.- Methods: DNA methylation.- RNA interference in mammalian systems: A practical approach.-Histone modifications: methods and techniques.- Characterization of the peroxisomal cycling receptor Pex5p import pathway.- Interaction of PEX3 and PEX19 visualized by fluorescence resonance energy transfer (FRET).- Gene Regulation of Peroxisomal Enzymes by Nutrients, Hormones and Nuclear Signalling Factors in Animal and Human Species.- Regulation of peroxisomal genes by dehydroepiandosterone and vit D.- Effect of DHEA supplementation on fatty acid and hormone levels in patients with X-linked adrenoleukodystrophy.- Dehydroepiandrosterone induction of the Abcd2 and Abcd3 genes encoding peroxisomal ABC transporters: implications for X-linked adrenoleukodystrophy.- Phytanic and pristanic acids are naturally occurring ligands.- Modifying the peroxisomes by cell & tissue culture.- Pharmacological induction of redundant genes for a therapy of X-ALD: phenylbutyrate and other compounds.- Peroxisomal fatty acid alpha- and beta-oxidation in health and disease: new insights.- Role of phytanoyl-CoA 2-hydroxylase in phytanic acid degradation.- Thiamine pyrophospate: an essential cofactor in the mammalian metabolism of 3-methyl-branched fatty acids - implications for thiamine deficiency?.- Metabolic regulation of peroxisomal and mitochondrial fatty acid oxidation.- Cholesterol biosynthesis and regulation: role of peroxisomes.- Peroxisome deficiency does not result in deficiency of enzymes involved in cholesterol biosynthesis.- Cholesterol regulates ABCD2 gene expression: implication for X-linked adrenoleuko-dystrophy.- Regulation of farnesyl diphosphate synthase gene expression by fatty acids.- Plasmalogens, docosahexaenoic acid and neurological disorders.- Targeted disruption of ether lipid synthesis in mice.- Evaluation of the preventive effect of glyceryl trioleate-trierucate(Lorenzo's oil) therapy in presymptomatic X-linked adrenoleukodystrophy. Results of two concurrent studies.- Author Index.
