Juvenile Huntington chorea

Goebel, Hans H.; Heipertz, R.; Scholz, Wolfgang; Iqbal, Khalid; Tellez-Nagel, Isabel

doi:10.1212/wnl.28.1.23

Cited by 101 publications

(45 citation statements)

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“…Fatty acid composition of SM from human cerebral white matter was reported to be abnormal in patients with juvenile and adult HD, with a shift toward shorter chain fatty acid. 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].…”

Section: Huntington's Diseasementioning

confidence: 94%

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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Section: Huntington's Diseasementioning

confidence: 94%

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

et al. 2010

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“…In platelets, one study reported decreased complex I activity and no change in the activities of complexes II-III and IV (Parker et al 1990a). Also ultrastructural abnormalities in mitochondria have been described in HD cortical tissue (Goebel et al 1978;Gardian and Vecsei 2004).…”

Section: Mitochondrial Involvement In Huntington's Diseasementioning

confidence: 99%

Mitochondria and Neurodegeneration

et al. 2007

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Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question "is mitochondrial dysfunction a necessary step in neurodegeneration?" is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.

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“…The principal indicator of an energetic involvement in the disease process is the observation of insidious weight loss in Huntington's disease patients despite a sustained caloric intake (O'Brien et al, 1990). Subsequently, positron emission tomography (PET) and biochemical studies in postmortem brain have shown selective metabolic defects in brain regions targeted by the disease, and mitochondrial abnormalities in Huntington's disease have been identified in ultrastructural studies of cortical biopsies from juvenile and adult-onset Huntington's disease cases (Goebel et al, 1978).…”

Section: A Bioenergetic Defectsmentioning

confidence: 99%

Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders

Browne¹

2003

PsycEXTRA Dataset

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Weill Medical College of Cornell university New York, New York 10021 E-Mail: sub2001@med.cornell.edu This project aims to determine the roles of bioenergetic dysfunction and oxidative stress in mechanisms of neurodegeneration in Huntingtons disease (HD) and familial amyotrophic lateral sclerosis. Studies in this second year extended the first year's investigations into cerebral glucose metabolism in mutant mouse models of HD. We found increases in cerebral glucose use in forebrain regions of 4 month-old Hdh "knock-in" mice expressing a mutant 92 glutamine stretch in huntingtin protein (Hdh Q92 ), relative to levels in wild-type mice (Hdh Q7 ). Metabolic changes precede pathologic changes and show a gene-dosage effect, homozygote Hdh Q92 mice showing larger magnitude changes than heterozygotes. We attempted to measure similar parameters in R6/2 HD mice, but experiments were hindered by the diabetic profile of these mice. However, findings in another HD mouse model (N171-82Q) also show pre-symptomatic cerebral glucose use elevations associated with the gene mutation. Results from years 1 and 2 suggest that mutant huntingtin expression induces metabolic abnormalities that precede symptom onset and pathological events in these mouse HD models. Further, the occurrence of metabolic changes is dependent on poly glutamine repeat length and gene dosage. These findings represent significant progress towards the original goals of this proposal. Where copyrighted material is quoted, permission has been obtained to use such material. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)U SUBJECT TERMSWhere material from documents designated for limited distribution is quoted, permission has been obtained to use the material.Citations of commercial organizations and trade names in this report do not constitute an official Department of Army endorsement or approval of the products or services of these organizations.*>* * S In conducting research using animals, the investigator(s) adhered to the "Guide for the Care and Use of Laboratory Animals," prepared by the Committee on Care and use of Laboratory Animals of the Institute of Laboratory Resources, national Research Council (NIH Publication No. 86-23, Revised 1985).For the protection of human subjects, the investigator(s) adhered to policies of applicable Federal Law 45 CFR 46.In conducting research utilizing recombinant DNA technology, the...

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Juvenile Huntington chorea

Cited by 101 publications

References 0 publications

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

Mitochondria and Neurodegeneration

Bioenergetic Defects and Oxidative Damage in Transgenic Mouse Models of Neurodegenerative Disorders

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