Dysmyelinogenesis in animal model of GM1 gangliosidosis

Kaye, Edward M.; Alroy, Joseph; Raghavan, Subharekha; Schwarting, Gerald A.; Adelman, Lester S.; Runge, Val M.; Gelblum, Dafna; Thalhammer, Johann G.; Zúñiga, Gonzalo

doi:10.1016/0887-8994(92)90361-2

Cited by 58 publications

(42 citation statements)

References 21 publications

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“…[17][18][19][20] Many of these phenomena have been attributed to ganglioside storage, albeit the underlying molecular effectors are still unknown. Neuronal cell death and demyelination occur in some of these LSDs [21][22][23] and are often accompanied by astrogliosis and microgliosis that appear mostly in areas of severe neuronal vacuolation. [24][25][26] The presence of reactive astrocytes is indicative of an elicited neuroinflammatory response, and the biochemical heterogeneity and adaptive plasticity may reflect differences in microenvironmental cues, such as the combination of cytokines, growth factors, adhesion molecules, and other signals emanating from injured neurons, activated microglia, endothelial cells, and vascular components.…”

Section: Metabolism Of Gangliosidesmentioning

confidence: 99%

Gangliosides as apoptotic signals in ER stress response

d’Azzo

Tessitore²,

Sano

2006

Cell Death Differ

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Renewed attention has been given lately to gangliosides and to their function as intracellular messengers of the adaptive responses to stress. Gangliosides are vital components of cell membranes; therefore, deleterious consequences can result from changes in their chemical composition and concentration, that is, membrane dynamics and structure can be altered as can the behavior of other membrane proteins. The importance of gangliosides in human health is evident in neurodegenerative diseases associated with defects in their degradation. As key modulators of intracellular calcium flux, gangliosides are involved in cellular processes downstream of calcium signaling. In this review, we focus on the effect of ganglioside accumulation on the endoplasmic reticulum calcium homeostasis and on the integrity of the mitochondrial membranes. We discuss how these events elicit an apoptotic program that ultimately leads to cell death. Owing to interorganelle crosstalk, these events are not necessarily self-contained, and gangliosides may serve as the common factor.

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Section: Metabolism Of Gangliosidesmentioning

confidence: 99%

Gangliosides as apoptotic signals in ER stress response

d’Azzo

Tessitore²,

Sano

2006

Cell Death Differ

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“…We found a significant decrease in cerebrosides and sulfatides in the forebrains of the R6/1 transgenic mice (Table 4; HPTLC plates not shown). Interestingly, these are myelin-enriched lipids (Sandhoff et al, 1971,Seyfried and Yu, 1980,Kaye et al, 1992 and this decrease may be suggestive of abnormalities in myelin content in the R6/1 transgenic mouse model of HD. Our detection method did not show differences in cholesterol content between the R6/1 transgenic mice and wild type controls, as previously suggested in other models of HD (Sipione et al, 2002,Valenza et al, 2005.…”

Section: Neutral and Acidic Lipid Content And Distribution In The R6/mentioning

confidence: 99%

Glycolipid and ganglioside metabolism imbalances in Huntington's disease

Desplats

Denny

Kass

et al. 2007

Neurobiology of Disease

122

120

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We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington's disease (HD) mice using a custom designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD patients. Many of these genes show differential regional expression within the CNS, as indicated by in situ hybridization analysis, suggesting region-specific regulation of this system in the brain. We further show disrupted patterns of glycolipids (acidic and neutral lipids) and/ or ganglioside levels in both the forebrain of the R6/1 transgenic mice and caudate samples from human HD subjects. These findings reveal novel disruptions in glycolipid/ganglioside metabolic pathways in the pathology of HD and suggest that the development of new targets to restore glycosphingolipid balance may act to ameliorate some symptoms in HD.

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“…This model is of interest in testing potential therapeutic strategies. GM1 gangliosidosis has also been identified in cattle [82], dogs [164,165], and sheep [166]. Animals are clinically similar to the juvenile (type 2) form of the disease in humans [167].…”

Section: Models Of Hereditary Ataxiasmentioning

confidence: 99%

“…Mice homozygous for the jittery mutation exhibit severe trunk and limb ataxia. They die of dehydration and starvation by 3-4 weeks of age [164]. Jittery is caused by a mutagenic B1 insertion into exon 4 of the Atcay gene [69].…”

Section: Models Of Hereditary Ataxiasmentioning

confidence: 99%

Animal Models of Human Cerebellar Ataxias: a Cornerstone for the Therapies of the Twenty-First Century

Manto

Marmolino

2009

Cerebellum

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Cerebellar ataxias represent a group of disabling neurological disorders. Our understanding of the pathogenesis of cerebellar ataxias is continuously expanding. A considerable number of laboratory animals with neurological mutations have been reported and numerous relevant animal models mimicking the phenotype of cerebellar ataxias are becoming available. These models greatly help dissecting the numerous mechanisms of cerebellar dysfunction, a major step for the assessment of therapeutics targeting a given deleterious pathway and for the screening of old or newly synthesized chemical compounds. Nevertheless, differences between animal models and human disorders should not be overlooked and difficulties in terms of characterization should not be occulted. The identification of the mutations of many hereditary ataxias, the development of valuable animal models, and the recent identifications of the molecular mechanisms underlying cerebellar disorders represent a combination of key factors for the development of anti-ataxic innovative therapies. It is anticipated that the twenty-first century will be the century of effective therapies in the field of cerebellar ataxias. The animal models are a cornerstone to reach this goal.

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Dysmyelinogenesis in animal model of GM1 gangliosidosis

Cited by 58 publications

References 21 publications

Gangliosides as apoptotic signals in ER stress response

Gangliosides as apoptotic signals in ER stress response

Glycolipid and ganglioside metabolism imbalances in Huntington's disease

Animal Models of Human Cerebellar Ataxias: a Cornerstone for the Therapies of the Twenty-First Century

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