Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió acceptadaData de publicació
Tots els drets reservats
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/140347
Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications.
Matèries (anglès)
Citació
Citació
RODRIGUEZ-RODRIGUEZ, Patricia, SANDEBRING-MATTON, Anna, MERINO-SERRAIS, Paula, PARRADO-FERNANDEZ, Cristina, RABANO, Alberto, WINBLAD, Bengt, AVILA, Jesús, FERRER, Isidro (ferrer abizanda), CEDAZO-MÍNGUEZ, Ángel. Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons. _Brain_. 2017. Vol. 40, núm. 12, pàgs. 3269-3285. [consulta: 21 de gener de 2026]. ISSN: 0006-8950. [Disponible a: https://hdl.handle.net/2445/140347]