Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer's disease: A possible effect on APP processing

N. C. Inestrosa, C. Tapia-Rojas, T. N. Griffith, F. J. Carvajal, M. J. Benito, A. Rivera-Dictter, A. R. Alvarez, F. G. Serrano, J. L. Hancke, P. V. Burgos, J. Parodi, L. Varela-Nallar

Resultado de la investigación: Contribución a una revistaArtículo

45 Citas (Scopus)

Resumen

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ) accumulation and synaptic alterations. Previous studies indicated that hyperforin, a component of the St John's Wort, prevents Aβ neurotoxicity and some behavioral impairments in a rat model of AD. In this study we examined the ability of Tetrahydrohyperforin (IDN5607), a stable hyperforin derivative, to prevent the cognitive deficit and synaptic impairment in an in vivo model of AD. In double transgenic APPswe/PSEN1ΔE9 mice, IDN5706 improves memory and prevents the impairment of synaptic plasticity in a dose-dependent manner, inducing a recovery of long-term potentiation. In agreement with these findings, IDN5706 prevented the decrease in synaptic proteins in hippocampus and cortex. In addition, decreased levels of tau hyperphosphorylation, astrogliosis, and total fibrillar and oligomeric forms of Ab were determined in double transgenic mice treated with IDN5706. In cultured cells, IDN5706 decreased the proteolytic processing of the amyloid precursor protein that leads to Ab peptide generation. These findings indicate that IDN5706 ameliorates AD neuropathology and could be considered of therapeutic relevance in AD treatment.

Idioma originalInglés
Número de artículoe20
PublicaciónTranslational Psychiatry
Volumen1
DOI
EstadoPublicada - 12 jul 2011

Áreas temáticas de ASJC Scopus

  • Psiquiatría y salud mental
  • Psiquiatría biológica
  • Neurociencia celular y molecular

Huella Profundice en los temas de investigación de 'Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer's disease: A possible effect on APP processing'. En conjunto forman una huella única.

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    Inestrosa, N. C., Tapia-Rojas, C., Griffith, T. N., Carvajal, F. J., Benito, M. J., Rivera-Dictter, A., Alvarez, A. R., Serrano, F. G., Hancke, J. L., Burgos, P. V., Parodi, J., & Varela-Nallar, L. (2011). Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer's disease: A possible effect on APP processing. Translational Psychiatry, 1, [e20]. https://doi.org/10.1038/tp.2011.19