Erythrocyte glycolipids in Huntington's chorea

Wherrett, John R.; Brown, B. L.

doi:10.1212/wnl.19.5.489

Cited by 28 publications

(9 citation statements)

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“…This is consistent with reports by Booth (1967) and Wherrett (1969) but at variance with the reports by Edgar et al (1965) andHooghwinkel et al (1966). The reason for this discrepancy is obscure, but it is tempting to examine the possible part played by peroxidation products of poly-unsaturated fatty-acids, vchieh arc known to give a colored compound when reacting with thio-barbituratic acid.…”

Section: Discussionsupporting

confidence: 88%

Sialic acid in erythrocytes of patients with amaurotic idiocy and Huntington's chorea

Pronk¹,

Hooyen-Bosma²,

Edgar³

1972

Hum Genet

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Section: Discussionsupporting

confidence: 88%

Sialic acid in erythrocytes of patients with amaurotic idiocy and Huntington's chorea

Pronk¹,

Hooyen-Bosma²,

Edgar³

1972

Hum Genet

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“…A decreased ratio of sphingomyelins to lipids across disease stages could indicate an increased vulnerability and damage of nerve cell axons. Even though the role of sphingolipids and gangliosides in brain damage has been investigated since the 1970s (Wherrett and Brown 1969 ; Higatsberger et al 1981 ; Heipertz et al 1977 ) it is not until recently that strong evidence has been presented in support of the role of gangliosides and their biosynthetic genes in autophagic and apoptotic signaling (Takamura et al 2008 ; Desplats et al 2007 ). Additionally, the ratio of arginine to carnitine metabolites was among the top results for the two group (HD vs. controls) metabolite pair analysis with modest p-gain values.…”

Section: Discussionmentioning

confidence: 99%

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington’s disease peripheral blood samples

et al. 2016

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IntroductionMetabolic changes have been frequently associated with Huntington’s disease (HD). At the same time peripheral blood represents a minimally invasive sampling avenue with little distress to Huntington’s disease patients especially when brain or other tissue samples are difficult to collect.ObjectivesWe investigated the levels of 163 metabolites in HD patient and control serum samples in order to identify disease related changes. Additionally, we integrated the metabolomics data with our previously published next generation sequencing-based gene expression data from the same patients in order to interconnect the metabolomics changes with transcriptional alterations.MethodsThis analysis was performed using targeted metabolomics and flow injection electrospray ionization tandem mass spectrometry in 133 serum samples from 97 Huntington’s disease patients (29 pre-symptomatic and 68 symptomatic) and 36 controls.ResultsBy comparing HD mutation carriers with controls we identified 3 metabolites significantly changed in HD (serine and threonine and one phosphatidylcholine—PC ae C36:0) and an additional 8 phosphatidylcholines (PC aa C38:6, PC aa C36:0, PC ae C38:0, PC aa C38:0, PC ae C38:6, PC ae C42:0, PC aa C36:5 and PC ae C36:0) that exhibited a significant association with disease severity. Using workflow based exploitation of pathway databases and by integrating our metabolomics data with our gene expression data from the same patients we identified 4 deregulated phosphatidylcholine metabolism related genes (ALDH1B1, MBOAT1, MTRR and PLB1) that showed significant association with the changes in metabolite concentrations.ConclusionOur results support the notion that phosphatidylcholine metabolism is deregulated in HD blood and that these metabolite alterations are associated with specific gene expression changes.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1084-8) contains supplementary material, which is available to authorized users.

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“…However, this event does not seem to be specific for this disease, but rather an index of disturbed myelination and demyelination, since it has been associated with an immature myelin and detected also in young children and in several cases of non-specific brain damage associated with demyelination [276,277]. On the other hand, changes in the GSL composition have been observed in erythrocytes from HD patients [278], and a marked reduction in the ganglioside concentration was detected in the striatum of HD human brains and in rat brains after lesioning by intrastriatal injection of kainic acid [279]. More recently, abnormal expression of the genes encoding several glycosyltransferases involved in ganglioside biosynthesis has been reported in the striatum of hexon 1 transgenic Huntington's disease mice (R6/1 mice) and in post-mortem caudate from human HD patients [280].…”

Section: Huntington's Diseasementioning

confidence: 95%

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

et al. 2010

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Sphingolipids are polar membrane lipids present as minor components in eukaryotic cell membranes. Sphingolipids are highly enriched in nervous cells, where they exert important biological functions. They deeply affect the structural and geometrical properties and the lateral order of cellular membranes, modulate the function of several membrane-associated proteins, and give rise to important intra- and extracellular lipid mediators. Sphingolipid metabolism is regulated along the differentiation and development of the nervous system, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system: sphingolipids in the nervous system participate to several signaling pathways controlling neuronal survival, migration, and differentiation, responsiveness to trophic factors, synaptic stability and synaptic transmission, and neuron-glia interactions, including the formation and stability of central and peripheral myelin. In several neurodegenerative diseases, sphingolipid metabolism is deeply deregulated, leading to the expression of abnormal sphingolipid patterns and altered membrane organization that participate to several events related to the pathogenesis of these diseases. The most impressive consequence of this deregulation is represented by anomalous sphingolipid-protein interactions that are at least, in part, responsible for the misfolding events that cause the fibrillogenic and amyloidogenic processing of disease-specific protein isoforms, such as amyloid beta peptide in Alzheimer's disease, huntingtin in Huntington's disease, alpha-synuclein in Parkinson's disease, and prions in transmissible encephalopathies. Targeting sphingolipid metabolism represents today an underexploited but realistic opportunity to design novel therapeutic strategies for the intervention in these diseases.

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Erythrocyte glycolipids in Huntington's chorea

Cited by 28 publications

References 0 publications

Sialic acid in erythrocytes of patients with amaurotic idiocy and Huntington's chorea

Sialic acid in erythrocytes of patients with amaurotic idiocy and Huntington's chorea

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington’s disease peripheral blood samples

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

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