L444P Gba1 mutation increases formation and spread of α-synuclein deposits in mice injected with mouse α-synuclein pre-formed fibrils.
PLoS One
; 15(8): e0238075, 2020.
Article
en En
| MEDLINE
| ID: mdl-32833982
ABSTRACT
Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synuclein accumulation, a hallmark of Parkinson disease, is not fully understood. Following our recent finding that Gba1 mutations lead to increased α-synuclein accumulation in mice, we have studied the effects of a single injection of mouse α-synuclein pre-formed fibrils into the striatum of Gba1 mice that carry a L444P knock-in mutation. We found significantly greater formation and spread of α-synuclein inclusions in Gba1-transgenic mice compared to wild-type controls. This indicates that the Gba1 L444P mutation accelerates α-synuclein pathology and spread.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Alfa-Sinucleína
/
Técnicas de Sustitución del Gen
/
Agregado de Proteínas
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Glucosilceramidasa
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Mutación
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2020
Tipo del documento:
Article