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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.
Neurosci Lett. 2009 Mar 13; 452(2):90-5.NL

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+Show Affiliations

Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19154776

Citation

Mei, Zhengrong, et al. "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." Neuroscience Letters, vol. 452, no. 2, 2009, pp. 90-5.
Mei Z, Zhang F, Tao L, et al. 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. Neurosci Lett. 2009;452(2):90-5.
Mei, Z., Zhang, F., Tao, L., Zheng, W., Cao, Y., Wang, Z., Tang, S., Le, K., Chen, S., Pi, R., & Liu, P. (2009). 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. Neuroscience Letters, 452(2), 90-5. https://doi.org/10.1016/j.neulet.2009.01.013
Mei Z, et al. 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. Neurosci Lett. 2009 Mar 13;452(2):90-5. PubMed PMID: 19154776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mei,Zhengrong, AU - Zhang,Fangyan, AU - Tao,Liang, AU - Zheng,Wenhua, AU - Cao,Yingnan, AU - Wang,Zhaohe, AU - Tang,Shu, AU - Le,Kang, AU - Chen,Shaorui, AU - Pi,Rongbiao, AU - Liu,Peiqing, Y1 - 2009/01/13/ PY - 2008/11/06/received PY - 2008/12/29/revised PY - 2009/01/07/accepted PY - 2009/1/22/entrez PY - 2009/1/22/pubmed PY - 2009/6/30/medline SP - 90 EP - 5 JF - Neuroscience letters JO - Neurosci. Lett. VL - 452 IS - 2 N2 - 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. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/19154776/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(09)00046-9 DB - PRIME DP - Unbound Medicine ER -