TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE

Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii...

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Main Author: Allsbrook, Matthew
Format: Others
Published: VCU Scholars Compass 2009
Subjects:
Online Access:http://scholarscompass.vcu.edu/etd/1858
http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2857&context=etd
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spelling ndltd-vcu.edu-oai-scholarscompass.vcu.edu-etd-28572017-03-17T08:31:10Z TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE Allsbrook, Matthew Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic effect of Triptolide on the neuropathology and deficits of spatial 6 learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) doubletransgenic mice, a well established Alzheimer’s disease (AD) mouse model. After treatment of APP/PS1 mice with Triptolide (40μg/kg, three times weekly,), initiated when the mice were 5 months old, for as little as 8 weeks, significant decrease in β-amyloid (Aβ) deposition and microglia activation was observed. Moreover, Triptolide treatment robustly rescued spatial memory deficits observed in APP/PS1 mice. However, APP processing, tau hyperphosphorylation, and the activities of the two major kinases involved in tau hyperphosphorylation, cyclin dependent kinase 5 (cdk5) and glycogen synthase kinase 3β (GSK3β) were not affected by the Triptolide treatment. Based on the recent finding for the inhibitory effect of Triptolide on Aβ-induced production of pro-inflammatory cytokines from microglia, we propose that Triptolide treatment may have beneficial properties in halting glial activation and help restore an immune system that fights plaque deposition. Although the exact mechanism of action has yet to be deduced, the increase in APP CTFs while having a significant decrease in amyloid plaque deposition suggests that alterations in gamma secretase activity may be a possible answer. Currently, these results support the use of Triptolide as an effective therapeutic to prevent the progression of Alzheimer’s disease. 2009-07-01T07:00:00Z text application/pdf http://scholarscompass.vcu.edu/etd/1858 http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2857&context=etd © The Author Theses and Dissertations VCU Scholars Compass Alzheimer's Disease triptolide APP processing microglia Medical Pharmacology Medical Sciences Medicine and Health Sciences
collection NDLTD
format Others
sources NDLTD
topic Alzheimer's Disease
triptolide
APP processing
microglia
Medical Pharmacology
Medical Sciences
Medicine and Health Sciences
spellingShingle Alzheimer's Disease
triptolide
APP processing
microglia
Medical Pharmacology
Medical Sciences
Medicine and Health Sciences
Allsbrook, Matthew
TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE
description Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic effect of Triptolide on the neuropathology and deficits of spatial 6 learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) doubletransgenic mice, a well established Alzheimer’s disease (AD) mouse model. After treatment of APP/PS1 mice with Triptolide (40μg/kg, three times weekly,), initiated when the mice were 5 months old, for as little as 8 weeks, significant decrease in β-amyloid (Aβ) deposition and microglia activation was observed. Moreover, Triptolide treatment robustly rescued spatial memory deficits observed in APP/PS1 mice. However, APP processing, tau hyperphosphorylation, and the activities of the two major kinases involved in tau hyperphosphorylation, cyclin dependent kinase 5 (cdk5) and glycogen synthase kinase 3β (GSK3β) were not affected by the Triptolide treatment. Based on the recent finding for the inhibitory effect of Triptolide on Aβ-induced production of pro-inflammatory cytokines from microglia, we propose that Triptolide treatment may have beneficial properties in halting glial activation and help restore an immune system that fights plaque deposition. Although the exact mechanism of action has yet to be deduced, the increase in APP CTFs while having a significant decrease in amyloid plaque deposition suggests that alterations in gamma secretase activity may be a possible answer. Currently, these results support the use of Triptolide as an effective therapeutic to prevent the progression of Alzheimer’s disease.
author Allsbrook, Matthew
author_facet Allsbrook, Matthew
author_sort Allsbrook, Matthew
title TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE
title_short TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE
title_full TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE
title_fullStr TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE
title_full_unstemmed TRIPTOLIDE IS A POTENTIAL THERAPEUTIC AGENT FOR ALZHEIMER’S DISEASE
title_sort triptolide is a potential therapeutic agent for alzheimer’s disease
publisher VCU Scholars Compass
publishDate 2009
url http://scholarscompass.vcu.edu/etd/1858
http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2857&context=etd
work_keys_str_mv AT allsbrookmatthew triptolideisapotentialtherapeuticagentforalzheimersdisease
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