Neuronal intranuclear hyaline inclusion disease with polyglutamine-immunoreactive inclusions.
Acta Neuropathol
; 99(5): 589-94, 2000 May.
Article
en En
| MEDLINE
| ID: mdl-10805106
Neuronal intranuclear hyaline inclusion disease (NIHID) is a group of neurodegenerative disorders characterized by the presence of intranuclear inclusions in neurons (NIs). We report here clinicopathological findings of a 25-year-old female patient who died after 13 years of a clinical course characterized by progressive gait disturbance and movement disorders. Histological examination revealed widespread NIs with neuronal loss in restricted regions; neuronal loss was severe in the subthalamic nucleus, internal pallidum, substantia nigra, Edinger-Westphal nucleus and Purkinje cell layer. Quantification of the NIs combined with a graded evaluation of neuronal loss revealed an overall tendency for more severe neuronal loss to be accompanied by a lower frequency of NIs. A morphological similarity to the nuclear inclusions recently identified in several CAG repeat diseases prompted us to examine the immunolocalization of ubiquitin and expanded polyglutamine stretches, which demonstrated the presence of ubiquitin at the periphery of most NIs. An expanded polyglutamine stretch was seen in the center of limited number of NIs. These findings indicate that abnormal fragments such as expanded polyglutamine regions are incorporated into the inclusion, aggregated in its center, and thereby metabolized by a ubiquitin-dependent proteolytic pathway. Although it remains to be elucidated how the formation of NIs is related to neuronal degeneration, our findings suggest that NIs are formed in the process of sequestering or degrading abnormal protein fragments and formation of NIs may not be immediately toxic to neurons.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Cuerpos de Inclusión
/
Hialina
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Acta Neuropathol
Año:
2000
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Alemania