Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1.
Nat Neurosci
; 3(2): 157-63, 2000 Feb.
Article
en En
| MEDLINE
| ID: mdl-10649571
ABSTRACT
The expansion of an unstable CAG repeat causes spinocerebellar ataxia type 1 (SCA1) and several other neurodegenerative diseases. How polyglutamine expansions render the resulting proteins toxic to neurons, however, remains elusive. Hypothesizing that long polyglutamine tracts alter gene expression, we found certain neuronal genes involved in signal transduction and calcium homeostasis sequentially downregulated in SCA1 mice. These genes were abundant in Purkinje cells, the primary site of SCA1 pathogenesis; moreover, their downregulation was mediated by expanded ataxin-1 and occurred before detectable pathology. Similar downregulation occurred in SCA1 human tissues. Altered gene expression may be the earliest mediator of polyglutamine toxicity.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Regulación hacia Abajo
/
Expansión de Repetición de Trinucleótido
/
Ataxias Espinocerebelosas
/
Sistema de Transporte de Aminoácidos X-AG
/
Simportadores
/
Neuronas
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
Nat Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos