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 ... -  《-》

Fuzhisan Ameliorates the Memory Deficits in Aged SAMP8 Mice via Decreasing Aβ Production and Tau Hyperphosphorylation of the Hippocampus.

Zhang ZX ，Zhao RP ，Wang DS ，Li YB ... -  《-》

Atorvastatin ameliorates cognitive impairment, Aβ1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice.

Zhou D ，Liu H ，Li C ，Wang F ，Shi Y ，Liu L ，Zhao X ，Liu A ，Zhang J ，Wang C ，Chen Z ... -  《-》

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》

Melatonin ameliorates amyloid beta-induced memory deficits, tau hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3β pathway in the mouse hippocampus.

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of amyloid beta (Aβ) aggregation in the brain, and is considered to be the primary cause of cognitive dysfunction. Aβ aggregates lead to synaptic disorder, tau hyperphosphorylation, and neurodegeneration. In this study, the underlying neuroprotective mechanism of melatonin against Aβ1-42-induced neurotoxicity was investigated in the mice hippocampus. Intracerebroventricular (i.c.v.) Aβ1-42-injection triggered memory impairment, synaptic disorder, hyperphosphorylation of tau protein, and neurodegeneration in the mice hippocampus. After 24 hr of Aβ1-42 injection, the mice were treated with melatonin (10 mg/kg, intraperitonially) for 3 wks, reversed the Aβ1-42-induced synaptic disorder via increasing the level of presyanptic (Synaptophysin and SNAP-25) and postsynaptic protein [PSD95, p-GluR1 (Ser845), SNAP23, and p-CREB (Ser133)], respectively, and attenuated the Aβ1-42-induced memory impairment. Chronic melatonin treatment attenuated the hyperphosphorylation of tau protein via PI3K/Akt/GSK3β signaling by activating the p-PI3K, p-Akt (Ser 473) and p-GSK3β (Ser9) in the Aβ1-42-treated mice. Furthermore, melatonin decreased Aβ1-42 -induced apoptosis through decreasing the overexpression of caspase-9, caspase-3, and PARP-1 level. Additionally, the evaluation of immunohistochemical analysis of caspase-3, Fluorojade-B, and Nissl staining indicated that melatonin prevented neurodegeneration in Aβ1-42-treated mice. Our results demonstrated that melatonin has neuroprotective effect against Aβ1-42-induced neurotoxicity through decreasing memory impairment, synaptic disorder, tau hyperphosphorylation, and neurodegeneration via PI3K/Akt/GSK3β signaling in the Aβ1-42-treated mouse model of AD. On the basis of these results, we suggest that melatonin could be an effective, promising, and safe neuroprotective candidate for the treatment of progressive neurodegenerative disorders, such as AD.

Ali T ，Kim MO 《-》