PT  - JOURNAL ARTICLE
AU  - Ying Peng
AU  - Yanli Hu
AU  - Shaofeng Xu
AU  - Xianfang Rong
AU  - Jiang Li
AU  - PingPing Li
AU  - Ling Wang
AU  - Jinghua Yang
AU  - Xiaoliang Wang
TI  - Potassium 2-(1-Hydroxypentyl)-Benzoate Improves Memory Deficits and Attenuates Amyloid and <em>τ</em> Pathologies in a Mouse Model of Alzheimer's Disease
AID  - 10.1124/jpet.114.213140
DP  - 2014 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 361--374
VI  - 350
IP  - 2
4099  - http://jpet.aspetjournals.org/content/350/2/361.short
4100  - http://jpet.aspetjournals.org/content/350/2/361.full
SO  - J Pharmacol Exp Ther2014 Aug 01; 350
AB  - 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.