在不同年龄的AβPPswe/PS-1小鼠中，大黄酸huprine衍生物降低认知障碍，突触失效和淀粉样蛋白

Title:Rhein-Huprine Derivatives Reduce Cognitive Impairment, Synaptic Failure and Amyloid Pathology in AβPPswe/PS-1 Mice of Different Ages

Volume: 13 Issue: 9

Author(s): Felipe G. Serrano, Cheril Tapia-Rojas, Francisco J. Carvajal, Pedro Cisternas, Elisabet Viayna, Irene Sola, Diego Munoz-Torrero and Nibaldo C. Inestrosa

Affiliation:

关键词: 阿尔茨海默病动物模型，β-淀粉样蛋白肽，tau蛋白，大黄酸huprine衍生物，长时程增强，记忆。

摘要: Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) peptide plays a key role in synaptic impairment and memory decline associated with neuronal dysfunction and intra-neuronal accumulation of hyperphosphorylated tau protein. Two novel enantiopure rhein-huprine hybrids ((+)-1 and (–)-1) exhibit potent inhibitory effects against human acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), BACE-1 and both Aβ and tau antiaggregation activity in vitro and reduction on the amyloid precursor protein (APP) processing in vivo. Interestingly, in this work, we observed beneficial effects with both (+)- and (–)-1 in the reversion of the neuropathology presented in the AβPPswe/PS-1 Alzheimer´s model, including a reduction in the Aβ levels, tau phosphorylation and memory impairment with both treatments. Also, in young transgenic mice that present early symptoms of synaptic failure and memory loss, we found a protection of cognitive functions, including long-term potentiation (LTP) and a reduction of the neuro-inflammation by both (+)- and (–)-1. Furthermore, animals with an advanced disease (11month-old) present an exacerbate neurodegeneration that is reversed only with the dextrorotatory enantiomer. These studies indicated that rhein-huprine derivatives with multiple properties might have interesting therapeutic potential for AD.

Cite this article as:

Felipe G. Serrano, Cheril Tapia-Rojas, Francisco J. Carvajal, Pedro Cisternas, Elisabet Viayna, Irene Sola, Diego Munoz-Torrero and Nibaldo C. Inestrosa , Rhein-Huprine Derivatives Reduce Cognitive Impairment, Synaptic Failure and Amyloid Pathology in AβPPswe/PS-1 Mice of Different Ages, Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205012666151027141542