Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?
Mol Neurobiol
; 52(3): 1297-1314, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-25336039
ABSTRACT
Huntington disease is a dominantly inherited disease of the central nervous system. The mutational expansion of polyglutamine beyond a critical length produces a toxic gain of function in huntingtin and results in neuronal death. In the course of the disease, expanded huntingtin is proteolyzed, becomes abnormally folded, and accumulates in oligomers, fibrils, and microscopic inclusions. The aggregated forms of the expanded protein are structurally diverse. Structural heterogeneity may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective. When defined, the toxic structures could then specifically be targeted by prophylactic or therapeutic drugs aimed at inhibiting polyglutamine aggregation.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Enfermedad de Huntington
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Agregación Patológica de Proteínas
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Amiloide
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Proteínas del Tejido Nervioso
Límite:
Animals
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Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article