Abstract
The aim was to determine whether the neuroprotective effect of SIRT1 in Alzheimer’s disease (AD), due to inhibition of aggregation of the β-amyloid peptide (Aβ), involves activation of α7 nAChR. In present study, four-month-old APP/PS1 mice were administered resveratrol (RSV) or suramin once daily for two months, following which their spatial learning and memory were assessed using the Morris water maze test. Deposits of Aβ in vivo were detected by near-infrared imaging (NIRI) and confocal laser scanning. SH-SY5Y/APPswe cells were treated with RSV, suramin, U0126 or methyllycaconitine (MLA). Levels of proteins and mRNA were determined by Western blotting and qRT-PCR, respectively. The results show that activation of SIRT1 improved their spatial learning and memory and reduced the production and aggregation of Aβ in the hippocampus and cerebral cortex; whereas inhibition of SIRT1 had the opposite effects. In addition, activation of SIRT1 increased the levels of both α7 nAChR and αAPP in the brains these animals. Finally, activation of SIRT1 elevated the levels of pERK1/2, while inhibition of ERK1/2 counteracted the increase in α7 nAChR caused by RSV. These findings indicate that neuroprotection by SIRT1 may involve increasing levels of α7 nAChR through activation of the MAPK/ERK1/2 signaling pathway.
Highlights
Alzheimer’s disease (AD) currently afflicts more than 35 million people worldwide [1] and the Delphi study predicted that this number will rise to 42.3 million in 2020 and 81.1 million in 2040 [2]
Our results demonstrate that the neuroprotection afforded by SIRT1 may involve increasing expression of α7 nicotinic acetylcholine receptor (nAChR), by activating the MAPK/ERK1/2 signaling pathway
After two months of treatment with RSV or Suramin, the escape latency, number of platform crossings and time spent at the original position of the platforms in the Morris water maze differed between the groups of mice
Summary
Alzheimer’s disease (AD) currently afflicts more than 35 million people worldwide [1] and the Delphi study predicted that this number will rise to 42.3 million in 2020 and 81.1 million in 2040 [2]. This neurodegenerative disease is characterized by a number of neuropathological changes, including deposits of β-amyloid peptides (Aβ), neurofibrillary tangles, and large-scale loss of neuron [3]. The amyloid cascade hypothesis is supported by extensive experimental findings showing that aggregation of Aβ into fibrils and/or other selfassembling states is central to this process. An improved understanding of the molecular mechanisms underlying AD is necessary for the development of novel, more effective strategies for diagnosis and treatment
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