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 Aβ 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 Aβ peptide generation. These findings indicate that IDN5706 ameliorates AD neuropathology and could be considered of therapeutic relevance in AD treatment.
authors: Centro de Envejecimiento y Regeneración (CARE), Santiago, Chile. ninestrosa@bio.puc.cl
authors: N C
authors: NC
authors: Inestrosa
authors: C
authors: C
authors: Tapia-Rojas
authors: T N
authors: TN
authors: Griffith
authors: F J
authors: FJ
authors: Carvajal
authors: M J
authors: MJ
authors: Benito
authors: A
authors: A
authors: Rivera-Dictter
authors: A R
authors: AR
authors: Alvarez
authors: F G
authors: FG
authors: Serrano
authors: J L
authors: JL
authors: Hancke
authors: P V
authors: PV
authors: Burgos
authors: J
authors: J
authors: Parodi
authors: L
authors: L
authors: Varela-Nallar
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D010696:Phloroglucinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D053764:Presenilin-1 / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D013729:Terpenes; D016875:tau Proteins; D010696:Phloroglucinol; C001654:hyperforin