title: Lamin B1 mediated demyelination: Linking Lamins, Lipids and Leukodystrophies.
abstract: Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating disorder, is the only human disease that has been linked to mutations of the nuclear lamina protein, lamin B1, and is primarily caused by duplications of the LMNB1 gene. Why CNS myelin is specifically targeted and the mechanisms underlying ADLD are unclear. Recent work from our group has demonstrated that over expression of lamin B1 in oligodendrocytes, the myelin producing cells in the CNS, resulted in age dependent epigenetic modifications, transcriptional down-regulation of lipogenic gene expression and significant reductions of myelin-enriched lipids. Given the high lipid content of meylin, we hypothesize that lipid loss is one of the primary drivers of the demyelination phenotype. These results can, at least partially, explain the age dependence and cell type specificity in ADLD and are discussed in the context of the existing literature, in an attempt to delineate potential pathways underlying the disease phenotype.
authors.affiliation: a Department of Human Genetics , Graduate School of Public Health, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Quasar S
authors.initials: QS
authors.lastname: Padiath
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D009154:Mutation; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D034921:Lamin Type B
keywords: ADLD demyelination; Lamin B1; epigenetic modifications; leukodystrophy; lipid synthesis; nuclear lamina; nuclear structure; transcription