Your browser doesn't support javascript.
loading
Beta-sheet assembly of Tau and neurodegeneration in Drosophila melanogaster.
Passarella, Daniela; Goedert, Michel.
Afiliação
  • Passarella D; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Goedert M; MRC Laboratory of Molecular Biology, Cambridge, UK. Electronic address: mg@mrc-lmb.cam.ac.uk.
Neurobiol Aging ; 72: 98-105, 2018 12.
Article em En | MEDLINE | ID: mdl-30240946
ABSTRACT
The assembly of Tau into abundant ß-sheet-rich filaments characterizes human tauopathies. A pathological pathway leading from monomeric to filamentous Tau is believed to be at the heart of these diseases. However, in Drosophila models of Tauopathy, neurodegeneration has been observed in the absence of abundant Tau filaments. Here we investigated the role of Tau assembly into ß-sheets by expressing wild-type and Δ306-311 human Tau-383 in the retina and brain of Drosophila. We analyzed both lines for eye abnormalities, brain vacuolization, Tau phosphorylation and assembly, as well as climbing activity and survival. Flies expressing wild-type Tau-383 showed MC-1 staining, Tau hyperphosphorylation, and neurodegeneration. By contrast, flies expressing Δ306-311 Tau-383 had less MC-1 staining, reduced Tau hyperphosphorylation, and no detectable neurodegeneration. Their climbing ability and lifespan were similar to those of nontransgenic flies. Fluorescence spectroscopy after addition of Thioflavin T, a dye that interacts with ß-sheets, showed no signal when Δ306-311 Tau-383 was incubated with heparin. These findings demonstrate that the assembly of Tau into ß-sheets is necessary for neurodegeneration.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Retina / Encéfalo / Proteínas tau / Doenças Neurodegenerativas / Drosophila melanogaster Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Retina / Encéfalo / Proteínas tau / Doenças Neurodegenerativas / Drosophila melanogaster Idioma: En Ano de publicação: 2018 Tipo de documento: Article