Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies.
Hum Mol Genet
; 19(22): 4399-408, 2010 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-20817925
ABSTRACT
Neurodegeneration induced by abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau defines neurodegenerative tauopathies. Destabilization of microtubules by loss of tau function and filament formation by toxic gain of function are two mechanisms suggested for how abnormal tau triggers neuronal loss. Recent experiments in kinesin-1 deficient mice suggested that axonal transport defects can initiate biochemical changes that induce activation of axonal stress kinase pathways leading to abnormal tau hyperphosphorylation. Here we show using Drosophila and mouse models of tauopathies that reductions in axonal transport can exacerbate human tau protein hyperphosphorylation, formation of insoluble aggregates and tau-dependent neurodegeneration. Together with previous work, our results suggest that non-lethal reductions in axonal transport, and perhaps other types of minor axonal stress, are sufficient to induce and/or accelerate abnormal tau behavior characteristic of Alzheimer's disease and other neurodegenerative tauopathies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cinesinas
/
Proteínas tau
/
Tauopatías
/
Degeneración Nerviosa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos