Search results for "Leukodystrophy"
showing 10 items of 41 documents
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy
2019
Supplemental Digital Content is available in the text.
Myelin changes in Alexander disease
2018
Introduction: Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for glial fibrillary acidic protein (GFAP) have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood. Development: The most widespread hypothesis is that AxD develops when a gain-of-function mutation causes an increase in GFAP. However, this mechanism does not explain myelin loss, given that experimental models in which GFAP expression is normal or mutated do not exhibit myelin disorders. …
A morphometric study on sural nerves in metachromatic leucodystrophy.
1987
This study reexamines peripheral neuropathy in infantile, juvenile and adult metachromatic leuco-dystrophy. A computer-assisted method was used which gives more detailed information on abnormal fibre structure from scatter diagrams of the g ratio (axon diameter/fibre diameter). The data show marked and statistically significant reductions in sheath thickness, particularly for the thick myelinated fibres, and most severe in the juvenile and adult forms. This is interpreted as evidence of remodelling of virtually the entire fibre population, without a clear-cut selectivity for either thin or thick fibres.
Sulfatide excreting heterozygous carrier of juvenile metachromatic leukodystrophy or asymptomatic patient of adult metachromatic leukodystrophy.
1975
In a family with juvenile metachromatic leukodystrophy (sulfatide lipidosis) 2 patients showed residual arysulfatase A activities of 5--6%. The patients' healthy father was characterized biochemically by a 39% normal activity of leukocyte plus plasma arylsulfatase A. The father was further characterized by a high sulfatide excretion (0.2--0.5 mg/I urine) and, paradoxically, by a normal sulfatide degrading enzyme activity in vitro. This special carrier is suspected to be heterozygous for a) arylsulfatase A deficiency and b) arylsulfatase A (sulfatidase) lability. This presumed additional genetic defect could be the cause of the sulfatide excretion which, in turn, would be a sign of the precl…
Early auditory evoked potentials: developmental aspects and validity in neuropaediatric and audiologic disorders.
1984
Auditory evoked potentials and in this context especially five waves in the first 10 ms (early auditory evoked potentials = EAEP) are a diagnostic aid in topodiagnosis of posterior fossa diseases. This is due to waves I to V which arise along the acoustic nerve and in brain stem structures such as medulla, pons and mid-brain. Besides an indication about the site of a lesion in the posterior fossa, wave V allows an objective threshold determination. The present results were gained in normal children aged 1-3 years and in children with neuropaediatric and audiologic disorders.
LXR antagonists induce ABCD2 expression
2014
X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder characterized by the accumulation of very-long-chain fatty acids resulting from a beta-oxidation defect. Oxidative stress and inflammation are also key components of the pathogenesis. X-ALD is caused by mutations in the ABCDI gene, which encodes for a peroxisomal half ABC transporter predicted to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their beta-oxidation. Two homologous peroxisomal ABC transporters, ABCD2 and ABCD3 have been proven to compensate for ABCD1 deficiency when overexpressed. Pharmacological induction of these target genes could therefore represent an alternative ther…
A novel cell model to study the function of the adrenoleukodystrophy-related protein
2006
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder due to mutations in the ABCD1 (ALD) gene. ALDRP, the closest homolog of ALDP, has been shown to have partial functional redundancy with ALDP and, when overexpressed, can compensate for the loss-of-function of ALDP. In order to characterize the function of ALDRP and to understand the phenomenon of gene redundancy, we have developed a novel system that allows the controlled expression of the ALDRP-EGFP fusion protein (normal or non-functional mutated ALDRP) using the Tet-On system in H4IIEC3 rat hepatoma cells. The generated stable cell lines express negligible levels of endogenous ALDRP and doxycycline dosage-dependent lev…
A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system.
2012
The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is f…
Myelin Proteome Analysis: Methods and Implications for the Myelin Cytoskeleton
2012
Myelin, the multilayered membrane that enwraps and insulates neuronal axons for fast signal propagation, is a plasma membrane specialization of oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively. Here we provide our lab protocols for the puri fi cation of myelin from mouse brains and for gel-based and gel-free proteomic applications, as well as a brief discussion with respect to our current knowledge of the myelin cytoskeleton.
Rat adrenoleukodystrophy-related (ALDR) gene: full-length cDNA sequence and new insight in expression.
2001
X-linked adrenoleukodystrophy (X-ALD) is an inherited demyelinating disorder due to mutations in the ALD gene, which encodes a peroxisomal ABC half-transporter (ALDP). It has been suggested that ALDP assembles with ALDRP (adrenoleukodystrophy-related protein), a close homologous half-transporter, to form a functional heterodimer. For the first time full-length ALDRP cDNA (5.5 kb) was cloned, and 5' and 3' RACE analysis revealed that alternative usage of polyadenylation sites generates the two transcripts of 3.0 and 5.5 kb observed in the rat in Northern blot analysis. Southern blotting and chromosomal mapping demonstrated one ALDR locus in the rat genome. Characterisation of the 3' flanking…