A ß-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain.
Nat Commun
; 1: 110, 2010 Nov 02.
Article
en En
| MEDLINE
| ID: mdl-21045828
The discovery of α-synuclein (αS) mutations has made a major contribution to the understanding of the pathogenesis of α-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies (DLB). In contrast, less attention has been paid to ß-synuclein (ßS) mutations. In this paper, we show that transgenic (tg) mice expressing DLB-linked P123H ßS develop progressive neurodegeneration, as characterized by axonal swelling, astrogliosis and behavioural abnormalities, with memory disorder being more prominent than motor deficits. Furthermore, cross-breeding of P123H ßS tg mice with αS tg mice, but not with αS knockout mice, greatly enhanced neurodegeneration phenotypes. These results suggest that P123H ßS is pathogenic and cooperates with pathogenic αS to stimulate neurodegeneration in mouse brain, indicating a causative role of P123H ßS in familial DLB. Given the neuritic pathology of ßS in sporadic α-synucleinopathies, it appears that alteration of ßS can contribute to the pathogenesis of a broad range of α-synucleinopathies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido