Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau.
Science
; 370(6519)2020 11 20.
Article
en En
| MEDLINE
| ID: mdl-33004675
ABSTRACT
Neurodegeneration in Alzheimer's disease (AD) is closely associated with the accumulation of pathologic tau aggregates in the form of neurofibrillary tangles. We found that a p.Asp395Gly mutation in VCP (valosin-containing protein) was associated with dementia characterized neuropathologically by neuronal vacuoles and neurofibrillary tangles. Moreover, VCP appeared to exhibit tau disaggregase activity in vitro, which was impaired by the p.Asp395Gly mutation. Additionally, intracerebral microinjection of pathologic tau led to increased tau aggregates in mice in which p.Asp395Gly VCP mice was knocked in, as compared with injected wild-type mice. These findings suggest that p.Asp395Gly VCP is an autosomal-dominant genetic mutation associated with neurofibrillary degeneration in part owing to reduced tau disaggregation, raising the possibility that VCP may represent a therapeutic target for the treatment of AD.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas tau
/
Enfermedad de Alzheimer
/
Agregación Patológica de Proteínas
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Agregado de Proteínas
/
Proteína que Contiene Valosina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos