Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by aggregation of amyloid-β (Aβ) peptide in the hippocampus and cortex of brain. Neuroinflammation is considered a driving force of the progression of cognitive decline in AD. During the neuroinflammatory process, activated astrocytes and microglia induced by Aβ peptide produce pro-inflammatory factors and neurotoxins, which promote neurodegeneration in AD brain, eventually dementia. Thus, the suppression of glial over-activation in AD brain might result in therapeutic effect. Triptolide, a natural compound extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F., has shown anti-inflammatory effects. Whether triptolide exhibits preventive effects on AD-like pathology via anti-inflammatory action is unclear. The present study showed that intraperitoneal injection of triptolide (20 μg/kg) for 15 weeks markedly alleviated deficits in learning and memory, and prevented Aβ accumulation in the brain of AD transgenic mice (APP/PS1 mice). These results were accompanied by reduction in glial activation and contents of pro-inflammatory factors in the brain of APP/PS1 mice treated by triptolide compared to saline-treated APP/PS1 mice. In addition, we observed that the Mitogen-activated protein kinases (MAPKs, including p38, ERK and JNK) phosphorylation was also suppressed by treatment of triptolide in the brain of APP/PS1 mice. Taken together, our study suggests that molecular mechanisms underlying the therapeutic effects of triptolide on the AD model might involve inhibition of the neuroinflammation by suppressing MAPKs activity.
Keywords: Alzheimer’s disease, ERK, JNK, neuroinflammation, p38, triptolide.
Current Alzheimer Research
Title:Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice
Volume: 13 Issue: 3
Author(s): Yan-Qiu Cui, Qi Wang, Dong-Mei Zhang, Jun-Ya Wang, Bing Xiao, Yan Zheng and Xiao-Min Wang
Affiliation:
Keywords: Alzheimer’s disease, ERK, JNK, neuroinflammation, p38, triptolide.
Abstract: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by aggregation of amyloid-β (Aβ) peptide in the hippocampus and cortex of brain. Neuroinflammation is considered a driving force of the progression of cognitive decline in AD. During the neuroinflammatory process, activated astrocytes and microglia induced by Aβ peptide produce pro-inflammatory factors and neurotoxins, which promote neurodegeneration in AD brain, eventually dementia. Thus, the suppression of glial over-activation in AD brain might result in therapeutic effect. Triptolide, a natural compound extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F., has shown anti-inflammatory effects. Whether triptolide exhibits preventive effects on AD-like pathology via anti-inflammatory action is unclear. The present study showed that intraperitoneal injection of triptolide (20 μg/kg) for 15 weeks markedly alleviated deficits in learning and memory, and prevented Aβ accumulation in the brain of AD transgenic mice (APP/PS1 mice). These results were accompanied by reduction in glial activation and contents of pro-inflammatory factors in the brain of APP/PS1 mice treated by triptolide compared to saline-treated APP/PS1 mice. In addition, we observed that the Mitogen-activated protein kinases (MAPKs, including p38, ERK and JNK) phosphorylation was also suppressed by treatment of triptolide in the brain of APP/PS1 mice. Taken together, our study suggests that molecular mechanisms underlying the therapeutic effects of triptolide on the AD model might involve inhibition of the neuroinflammation by suppressing MAPKs activity.
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Cite this article as:
Cui Yan-Qiu, Wang Qi, Zhang Dong-Mei, Wang Jun-Ya, Xiao Bing, Zheng Yan and Wang Xiao-Min, Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice, Current Alzheimer Research 2016; 13 (3) . https://dx.doi.org/10.2174/156720501303160217122803
DOI https://dx.doi.org/10.2174/156720501303160217122803 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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