IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
artículos
Título:
Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies.
Autor/es:
FALZONE T; GUNAWARDENA S; MCCLEARY D; REIS G; GOLDSTEIN L
Revista:
HUMAN MOLECULAR GENETICS
Editorial:
OXFORD UNIV PRESS
Referencias:
Lugar: Oxford; Año: 2010 vol. 19 p. 4399 - 4408
ISSN:
0964-6906
Resumen:
Neurodegeneration induced by abnormal hyperphosphorylation and aggregation of themicrotubule-associatedprotein tau defines neurodegenerative tauopathies. Destabilization of microtubules by loss of tau function andfilament formation by toxic gain of function are twomechanisms suggested for how abnormal tau triggers neuronalloss. Recent experiments in kinesin-1 deficientmice suggested that axonal transport defects can initiate biochemicalchanges that induce activation of axonal stress kinase pathways leading to abnormal tauhyperphosphorylation. Here we show using Drosophila and mouse models of tauopathies that reductions inaxonal transport can exacerbate human tau protein hyperphosphorylation, formation of insoluble aggregatesand tau-dependent neurodegeneration. Together with previous work, our results suggest that non-lethalreductions in axonal transport, and perhaps other types of minor axonal stress, are sufficient to induce and/oraccelerateabnormal taubehavior characteristic of Alzheimer’s diseaseandotherneurodegenerativetauopathies.