| Cryptotanshinone, a compound from Salvia miltiorrhiza modulates amyloid precursor protein metabolism and attenuates beta-amyloid deposition through upregulating alpha-secretase in vivo and in vitro. | |
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MedLine Citation:
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PMID: 19154776 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The amyloid precursor protein (APP) is cleaved enzymatically by non-amyloidogenic and amyloidogenic pathways. alpha-Secretase cleaves APP within beta-amyloid protein (Abeta) sequence, resulting in the release of a secreted fragment of APP (sAPPalpha) and precluding Abeta generation. Cryptotanshinone (CTS), an active component of the medicinal herb Salvia miltiorrhiza, has been shown to improve learning and memory in several pharmacological models of Alzheimer's disease (AD). However, the effects of CTS on the Abeta plaque pathology and the APP processing in AD are unclear. Here we reported that CTS strongly attenuated amyloid plaque deposition in the brain of APP/PS1 transgenic mice. In addition, CTS significantly improved spatial learning and memory in APP/PS1 mice assessed by the Morris water maze testing. To define the exact molecular mechanisms involved in the beneficial effects of CTS, we investigated the effects of the CTS on APP processing in rat cortical neuronal cells overexpressing Swedish mutant human APP695. CTS was found to decrease Abeta generation in concentration-dependent (0-10muM) manner. Interestingly, the N-terminal APP cleavage product, sAPPalpha was markedly increased by CTS. Further study showed that alpha-secretase activity was increased by CTS. Taken together, our results suggested CTS improved the cognitive ability in AD transgenic mice and promoted APP metabolism toward the non-amyloidogenic products pathway in rat cortical neuronal cells. CTS shows a promising novel way for the therapy of AD. |
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Authors:
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Zhengrong Mei; Fangyan Zhang; Liang Tao; Wenhua Zheng; Yingnan Cao; Zhaohe Wang; Shu Tang; Kang Le; Shaorui Chen; Rongbiao Pi; Peiqing Liu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-13 |
Journal Detail:
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Title: Neuroscience letters Volume: 452 ISSN: 0304-3940 ISO Abbreviation: Neurosci. Lett. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-23 Completed Date: 2009-06-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600130 Medline TA: Neurosci Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 90-5 Citation Subset: IM |
Affiliation:
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Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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drug therapy*,
enzymology*,
physiopathology Amyloid Precursor Protein Secretases / drug effects*, metabolism Amyloid beta-Protein / drug effects, metabolism Amyloid beta-Protein Precursor / drug effects*, genetics, metabolism Animals Brain / drug effects, enzymology Cerebral Cortex / drug effects, enzymology Disease Models, Animal Dose-Response Relationship, Drug Drugs, Chinese Herbal / pharmacology Memory Disorders / drug therapy, enzymology, physiopathology Mice Mice, Inbred C57BL Mice, Transgenic Phenanthrenes / pharmacology* Presenilin-1 / genetics, metabolism Rats Salvia miltiorrhiza / chemistry Senile Plaques / drug effects, metabolism Up-Regulation / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein; 0/Amyloid beta-Protein Precursor; 0/Drugs, Chinese Herbal; 0/Phenanthrenes; 0/Presenilin-1; 0/Salvia extract; 35825-57-1/cryptotanshinone; EC 3.4.-/Amyloid Precursor Protein Secretases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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