Potassium 2-(1-hydroxypentyl)-benzoate improves memory deficits and attenuates amyloid and τ pathologies in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles. Dl-PHPB [potassium 2-(1-hydroxypentyl)-benzoate], has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia, and Aβ-induced animal models by inhibiting oxidative injury, neuronal apoptosis, and glial activation. The aim of the present study was to examine the effect of dl-PHPB on learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic AD mouse models (APP/PS1) and the mechanisms of dl-PHPB in reducing Aβ accumulation and τ phosphorylation. Twelve-month-old APP/PS1 mice were given 30 mg/kg dl-PHPB by oral gavage for 3 months. Dl-PHPB treatment significantly improved the spatial learning and memory deficits compared with the vehicle-treated APP/PS1 mice. In the meantime, dl-PHPB obviously reduced τ hyperphosphorylation at Ser199, Thr205, and Ser396 sites in APP/PS1 mice. This reduction was accompanied by APP phosphorylation reduction and protein kinase C activation. In addition, expression of cyclin-dependent kinase and glycogen synthase kinase 3β, the most important kinases involved in τ phosphorylation, was markedly decreased by dl-PHPB treatment. Phosphorylated protein kinase B and phosphoinositide 3-kinase levels of APP/PS1 mice were significantly reduced compared with levels in wild-type mice, and dl-PHPB reversed the reduction. The effects of dl-PHPB effecting a decrease in τ phosphorylation and kinase activation were further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP695. These data raised the possibility that dl-PHPB might be a promising multitarget neuronal protective agent for the treatment of AD.

Peng Y ，Hu Y ，Xu S ，Rong X ，Li J ，Li P ，Wang L ，Yang J ，Wang X ... -  《-》

L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimer's transgenic mice.

Peng Y ，Hu Y ，Xu S ，Li P ，Li J ，Lu L ，Yang H ，Feng N ，Wang L ，Wang X ... -  《-》

Potassium 2-(1-hydroxypentyl)-benzoate promotes long-term potentiation in Aβ1-42-injected rats and APP/PS1 transgenic mice.

Li PP ，Wang WP ，Liu ZH ，Xu SF ，Lu WW ，Wang L ，Wang XL ... -  《-》

FLZ alleviates the memory deficits in transgenic mouse model of Alzheimer's disease via decreasing beta-amyloid production and tau hyperphosphorylation.

Bao XQ ，Li N ，Wang T ，Kong XC ，Tai WJ ，Sun H ，Zhang D ... -  《PLoS One》

Fuzhisan ameliorates Aβ production and tau phosphorylation in hippocampal of 11month old APP/PS1 transgenic mice: A Western blot study.

Accumulation of amyloid-β (Aβ) peptide and deposition of hyperphosphorylated tau protein are two major pathological hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3β (GSK3β) is increasingly thought to play a pivotal role in the pathogenesis of AD, both as a regulator of the production of Aβ and through its well-established role on tau phosphorylation. The phosphoinositide 3 kinase (PI3K)/Akt pathway plays an import role in neuronal survival and cognitive function, and is known as an upstream element of GSK3β. Fuzhisan (FZS), a Chinese herbal complex prescription, has been used for the treatment of AD for over 20years, and is known to enhance the cognitive ability in AD patients as well as in AD model rats. However, it still remains unclear whether FZS is responsible for regulation of PI3K/AKT/GSK3β signaling and contributes to subsequent down-regulation of Aβ and phosphorylated tau. Thus, we treated APP/PS1 transgenic mice, a useful model of AD-related memory impairment, with FZS by intragastrical administration for 60days and Donepezil was used as a positive control. The results showed that treatment with FZS significantly reversed the memory deficit in the Tg APP/PS1 mice in the Morris water maze test. Moreover, FZS significantly attenuated Aβ production through inhibition of APP procession and phosphorylation of tau in the hippocampus of Tg APP/PS1 mice. In addition, FZS treatment also increased PI3K and pSer473-AKT levels, inhibited GSK3β activity by increasing phosphorylation of GSK3β at Ser9. These results indicated that the memory ameliorating effect of FZS may be, in part, by regulation the PI3K/AKT/GSK3β signaling which may contribute to down-regulation of Aβ and tau hyperphosphorylation.

Zhang ZX ，Zhao RP ，Wang DS ，Wang AN ... -  《-》