Intranuclear Neuronal Inclusions in Huntington's Disease and Dentatorubral and Pallidoluysian Atrophy: Correlation between the Density of Inclusions andIT15CAG Triplet Repeat Length
| Autor: | Joyce A. Kotzuk, Christopher A. Ross, Donald L. Price, Alan H. Sharp, Mark W. Becher, Stephen W. Davies, Gillian P. Bates |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Adult
Pathology medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Huntingtin Adolescent Nerve Tissue Proteins Striatum Protein aggregation Biology Globus Pallidus lcsh:RC321-571 Pathogenesis Huntington's disease Trinucleotide Repeats mental disorders medicine Humans Child Ubiquitins lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Aged Red Nucleus Inclusion Bodies Neurons Huntingtin Protein Neocortex Nuclear Proteins Middle Aged medicine.disease Glutamine medicine.anatomical_structure Huntington Disease Neurology nervous system Dentate Gyrus Atrophy Trinucleotide repeat expansion |
| Zdroj: | Neurobiology of Disease, Vol 4, Iss 6, Pp 387-397 (1998) |
| Popis: | Huntington's disease (HD) is caused by CAG triplet repeat expansion inIT15which leads to polyglutamine stretches in the HD protein product, huntingtin. The pathological hallmark of HD is the degeneration of subsets of neurons, primarily those in the striatum and neocortex. Specific morphological markers of affected cells have not been identified in patients with HD, although a unique intranuclear inclusion was recently reported in neurons of transgenic animals expressing a construct encoding the N-terminal part (including the glutamine repeat) of huntingtin (Davieset al., 1997). In order to understand the importance of this finding, we sought for comparable nuclear abnormalities in autopsy material from patients with HD. In all 20 HD cases examined, anti-ubiquitin and N-terminal huntingtin antibodies identified intranuclear inclusions in neurons and the frequency of these lesions correlated with the length of the CAG repeat inIT15. In addition, examination of material from the related HD-like triplet repeat disorder, dentatorubral and pallidoluysian atrophy, also revealed intranuclear neuronal inclusions. These findings suggest that intranuclear inclusions containing protein aggregates may be a common feature of the pathogenesis of glutamine repeat neurodegenerative disorders. |
| Databáze: | OpenAIRE |
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