Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology.
J Biol Chem
; 289(2): 956-67, 2014 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-24235150
ABSTRACT
Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Emaranhados Neurofibrilares
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Proteínas tau
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Endocitose
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido