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: Article

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 originalEnglish
Número de artículoe20
PublicaciónTranslational Psychiatry
Volumen1
DOI
EstadoPublished - 12 jul 2011

Huella dactilar

Alzheimer Disease
Phosphorylation
Aptitude
hyperforin
Neuronal Plasticity
Long-Term Potentiation
Amyloid beta-Protein Precursor
Amyloid
Neurodegenerative Diseases
Transgenic Mice
Cultured Cells
Hippocampus
Peptides
Proteins

ASJC Scopus subject areas

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

Citar esto

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. / 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: Translational Psychiatry. 2011 ; Vol. 1.
@article{14e88cfd3a934c7bac8e7e464d7243c1,
title = "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",
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.",
keywords = "Aβ neurotoxicity, App transgenic, Hypericum perforatum, IDN5706, Ltp, Phf-1 phosphorylation",
author = "Inestrosa, {N. C.} and C. Tapia-Rojas and Griffith, {T. N.} and Carvajal, {F. J.} and Benito, {M. J.} and A. Rivera-Dictter and Alvarez, {A. R.} and Serrano, {F. G.} and Hancke, {J. L.} and Burgos, {P. V.} and J. Parodi and L. Varela-Nallar",
year = "2011",
month = "7",
day = "12",
doi = "10.1038/tp.2011.19",
language = "English",
volume = "1",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",

}

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. / 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.

En: Translational Psychiatry, Vol. 1, e20, 12.07.2011.

Resultado de la investigación: Article

TY - JOUR

T1 - Tetrahydrohyperforin prevents cognitive deficit, Aβ deposition, tau phosphorylation and synaptotoxicity in the APPswe/PSEN1ΔE9 model of Alzheimer's disease

T2 - A possible effect on APP processing

AU - Inestrosa, N. C.

AU - Tapia-Rojas, C.

AU - Griffith, T. N.

AU - Carvajal, F. J.

AU - Benito, M. J.

AU - Rivera-Dictter, A.

AU - Alvarez, A. R.

AU - Serrano, F. G.

AU - Hancke, J. L.

AU - Burgos, P. V.

AU - Parodi, J.

AU - Varela-Nallar, L.

PY - 2011/7/12

Y1 - 2011/7/12

N2 - 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.

AB - 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.

KW - Aβ neurotoxicity

KW - App transgenic

KW - Hypericum perforatum

KW - IDN5706

KW - Ltp

KW - Phf-1 phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=79960365191&partnerID=8YFLogxK

U2 - 10.1038/tp.2011.19

DO - 10.1038/tp.2011.19

M3 - Article

C2 - 22832522

AN - SCOPUS:79960365191

VL - 1

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

M1 - e20

ER -