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

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere20
JournalTranslational Psychiatry
Volume1
DOIs
Publication statusPublished - 12 Jul 2011

Keywords

  • App transgenic
  • Aβ neurotoxicity
  • Hypericum perforatum
  • IDN5706
  • Ltp
  • Phf-1 phosphorylation

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this