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.

Abstract

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.

• Authors: Zhengrong Mei, Fangyan Zhang, Liang Tao, Wenhua Zheng, Yingnan Cao, Zhaohe Wang, Shu Tang, Kang Le, Shaorui Chen, Rongbiao Pi, Peiqing Liu
• Journal: Neuroscience letters (Neurosci Lett) Vol. 452 Issue 2 Pg. 90-5 (Mar 13 2009) ISSN: 0304-3940 [Print] Ireland
• PMID: 19154776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Camphanes
• Drugs, Chinese Herbal
• Phenanthrenes
• Presenilin-1
• danshen dripping pill
• cryptotanshinone
• Amyloid Precursor Protein Secretases

Topics

• Alzheimer Disease (drug therapy, enzymology, physiopathology)
• Amyloid Precursor Protein Secretases (drug effects, metabolism)
• Amyloid beta-Peptides (drug effects, metabolism)
• Amyloid beta-Protein Precursor (drug effects, genetics, metabolism)
• Animals
• Brain (drug effects, enzymology)
• Camphanes
• 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
• Panax notoginseng
• Phenanthrenes (pharmacology)
• Plaque, Amyloid (drug effects, metabolism)
• Presenilin-1 (genetics, metabolism)
• Rats
• Salvia miltiorrhiza (chemistry)
• Up-Regulation (drug effects, physiology)