The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
William B Rizzo - One of the best experts on this subject based on the ideXlab platform.
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Disturbed brain ether lipid metabolism and histology in Sjögren-Larsson syndrome
Journal of inherited metabolic disease, 2020Co-Authors: Pippa Staps, William B Rizzo, Frédéric M. Vaz, Marianna Bugiani, Martin Giera, Bram Heijs, Antoine H. C. Van Kampen, Mia L. Pras-raves, Marjolein Breur, Annemieke GroenAbstract:Sjogren-Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient Fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia, and ichthyosis. The accumulation of Fatty alcohols and Fatty Aldehydes has been demonstrated in plasma and skin but never in brain. Brain magnetic resonance imaging and spectroscopy studies, however, have shown an abundant lipid peak in the white matter of patients with SLS, suggesting lipid accumulation in the brain as well. Using histopathology, mass spectrometry imaging, and lipidomics, we studied the morphology and the lipidome of a postmortem brain of a 65-year-old female patient with genetically confirmed SLS and compared the results with a matched control brain. Histopathological analyses revealed structural white matter abnormalities with the presence of small lipid droplets, deficient myelin, and astrogliosis. Biochemically, severely disturbed lipid profiles were found in both white and gray matter of the SLS brain, with accumulation of Fatty alcohols and ether lipids. Particularly, long-chain unsaturated ether lipid species accumulated, most prominently in white matter. Also, there was a striking accumulation of odd-chain Fatty alcohols and odd-chain ether(phospho)lipids. Our results suggest that the central nervous system involvement in SLS is caused by the accumulation of Fatty alcohols leading to a disbalance between ether lipid and glycero(phospho)lipid metabolism resulting in a profoundly disrupted brain lipidome. Our data show that SLS is not a pure leukoencephalopathy, but also a gray matter disease. Additionally, the histopathological abnormalities suggest that astrocytes and microglia might play a pivotal role in the underlying disease mechanism, possibly contributing to the impairment of myelin maintenance.
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ORIGINAL PAPER Ichthyosis in Sjögren–Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion
2013Co-Authors: Mary L Williams, Daiquirie Crumrine, William B Rizzo, S’aulis D. M. A. Jennings, Peter M. EliasAbstract:Ó The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Sjögren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for Fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of Fatty Aldehydes and Fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren– Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/nonlamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren– Larsson syndrome, which localizes to the stratum corneu
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ichthyosis in sjogren larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion
Archives of Dermatological Research, 2010Co-Authors: William B Rizzo, Dana Saulis, Anitia M Jennings, Daiquirie Crumrine, Mary L WilliamsAbstract:Sjogren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for Fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of Fatty Aldehydes and Fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjogren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjogren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.
Mary L Williams - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL PAPER Ichthyosis in Sjögren–Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion
2013Co-Authors: Mary L Williams, Daiquirie Crumrine, William B Rizzo, S’aulis D. M. A. Jennings, Peter M. EliasAbstract:Ó The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Sjögren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for Fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of Fatty Aldehydes and Fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren– Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/nonlamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren– Larsson syndrome, which localizes to the stratum corneu
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ichthyosis in sjogren larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion
Archives of Dermatological Research, 2010Co-Authors: William B Rizzo, Dana Saulis, Anitia M Jennings, Daiquirie Crumrine, Mary L WilliamsAbstract:Sjogren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for Fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of Fatty Aldehydes and Fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjogren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjogren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.
Raphael A Zoeller - One of the best experts on this subject based on the ideXlab platform.
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isolation of animal cell mutants defective in long chain Fatty aldehyde dehydrogenase sensitivity to Fatty Aldehydes and schiff s base modification of phospholipids implications for sjogren larsson syndrome
Journal of Biological Chemistry, 1997Co-Authors: Paul F James, Raphael A ZoellerAbstract:Abstract Using tritium suicide, we have isolated a variant of the Chinese hamster ovary cell line, CHO-K1, that is deficient in long-chain Fatty alcohol:NAD+oxidoreductase (FAO; EC 1.1.1.192). Specifically, it was the Fatty aldehyde dehydrogenase component that was affected. The enzymatic deficiency found in this mutant strain, designated FAA.K1A, was similar to that displayed by fibroblasts from patients with Sjogren-Larsson syndrome (SLS), an inheritable neurocutaneous disorder. Complementation analyses suggested that the deficiency in Fatty alcohol oxidation in the FAA.K1A cells and the SLS fibroblasts is a result of lesions in homologous genes. The FAA.K1A cells were unable to convert long chain Fatty Aldehydes to the corresponding Fatty acids. This resulted in a hypersensitivity of the FAA.K1A cells to the cytotoxic effects of long chain Fatty Aldehydes. The difference between the mutant and wild-type cells was most obvious when using Fatty Aldehydes between 14 and 20 carbons, with the greatest difference between wild-type and mutant cells found when using octadecanal. Fibroblasts from a patient with SLS also displayed the hypersensitivity phenotype when compared with FAldDH+ human fibroblasts. In both CHO and human FAldDH− cell lines, addition of long chain Fatty Aldehydes to the medium caused a dramatic increase in aldehyde-modified phosphatidylethanolamine, presumably through Schiff’s base addition to the primary amine of the ethanolamine head group. When 25 μm hexadecanal was added to the growth medium, approximately 10% of the phosphatidylethanolamine was found in the Fatty aldehyde-modified form in FAA.K1A, although this was not observed in wild-type cells. Modified phosphatidylethanolamine could be detected in FAldDH− cells even when exogenous Fatty Aldehydes were not added to the medium. We propose a possible role for Fatty Aldehydes, or other aldehydic species, in mediating some of the symptoms associated with Sjogren-Larsson syndrome.
Daiquirie Crumrine - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL PAPER Ichthyosis in Sjögren–Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion
2013Co-Authors: Mary L Williams, Daiquirie Crumrine, William B Rizzo, S’aulis D. M. A. Jennings, Peter M. EliasAbstract:Ó The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Sjögren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for Fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of Fatty Aldehydes and Fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren– Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/nonlamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren– Larsson syndrome, which localizes to the stratum corneu
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ichthyosis in sjogren larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion
Archives of Dermatological Research, 2010Co-Authors: William B Rizzo, Dana Saulis, Anitia M Jennings, Daiquirie Crumrine, Mary L WilliamsAbstract:Sjogren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for Fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of Fatty Aldehydes and Fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjogren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjogren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.
Pedro Brites - One of the best experts on this subject based on the ideXlab platform.
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Plasmalogens and Fatty alcohols in rhizomelic chondrodysplasia punctata and Sjögren-Larsson syndrome
Journal of Inherited Metabolic Disease, 2015Co-Authors: Ana R. Malheiro, Tiago Ferreira Da Silva, Pedro BritesAbstract:Plasmalogens are a special class of ether-phospholipids, best recognized by their vinyl-ether bond at the sn -1 position of the glycerobackbone and by the observation that their deficiency causes rhizomelic chondrodysplasia punctata (RCDP). The complex plasmalogen biosynthetic pathway involves multiple enzymatic steps carried-out in peroxisomes and in the endoplasmic reticulum. The rate limiting step in the biosynthesis of plasmalogens resides in the formation of the Fatty alcohol responsible for the formation of an intermediate with an alkyl-linked moiety. The regulation in the biosynthesis of plasmalogens also takes place at this step using a feedback mechanism to stimulate or inhibit the biosynthesis. As such, Fatty alcohols play a relevant role in the formation of ether-phospholipids. These advances in our understanding of complex lipid biosynthesis brought two seemingly distinct disorders into the spotlight. Sjögren-Larsson syndrome (SLS) is caused by defects in the microsomal Fatty aldehyde dehydrogenase (FALDH) leading to the accumulation of Fatty alcohols and Fatty Aldehydes. In RCDP cells, the defect in plasmalogens is thought to generate a feedback signal to increase their biosynthesis, through the activity of Fatty acid reductases to produce Fatty alcohols. However, the enzymatic defects in either glyceronephosphate O-acyltransferase (GNPAT) or alkylglycerone phosphate synthase (AGPS) disrupt the biosynthesis and result in the accumulation of the Fatty alcohols. A detailed characterization on the processes and enzymes that govern these intricate biosynthetic pathways, as well as, the metabolic characterization of defects along the pathway should increase our understanding of the causes and mechanisms behind these disorders.
