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Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing.
J Alzheimers Dis. 2012; 31(1):207-23.JA

Abstract

Ginseng extracts show cognition-enhancing effects in Alzheimer's disease (AD) patients. However, little is known about the active components and molecular mechanisms of how ginseng exerts its effects. Recently, we isolated a novel lysophosphatidic acid (LPA) receptor-activating ligand from ginseng, gintonin. AD is caused by amyloid-β protein (Aβ) accumulation. Aβ is derived from amyloid-β protein precursors (AβPPs) through the amyloidogenic pathway. In contrast, non-amyloidogenic pathways produce beneficial, soluble AβPPα (sAβPPα). Here, we describe our investigations of the effect of gintonin on sAβPPα release, Aβ formation, Swedish-AβPP transfection-mediated neurotoxicity in SH-SY5Y neuroblastoma cells, and Aβ-induced neuropathy in mice. Gintonin promoted sAβPPα release in a concentration- and time-dependent manner. Gintonin action was also blocked by the Ca2+ chelator BAPTA, α-secretase inhibitor TAPI-2, and protein-trafficking inhibitor brefeldin. Gintonin decreased Aβ1-42 release and attenuated Aβ1-40-induced cytotoxicity in SH-SY5Y cells. Gintonin also rescued Aβ1-40-induced cognitive dysfunction in mice. Moreover, in a transgenic mouse AD model, long-term oral administration of gintonin attenuated amyloid plaque deposition as well as short- and long-term memory impairment. In the present study, we demonstrated that gintonin mediated the promotion of non-amyloidogenic processing to stimulate sAβPPα release to restore brain function in mice with AD. Gintonin could be a useful agent for AD prevention or therapy.

Authors+Show Affiliations

Ginsentology Research Laboratory, Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Korea.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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22543851

Citation

Hwang, Sung Hee, et al. "Gintonin, a Ginseng-derived Lysophosphatidic Acid Receptor Ligand, Attenuates Alzheimer's Disease-related Neuropathies: Involvement of Non-amyloidogenic Processing." Journal of Alzheimer's Disease : JAD, vol. 31, no. 1, 2012, pp. 207-23.
Hwang SH, Shin EJ, Shin TJ, et al. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. J Alzheimers Dis. 2012;31(1):207-23.
Hwang, S. H., Shin, E. J., Shin, T. J., Lee, B. H., Choi, S. H., Kang, J., Kim, H. J., Kwon, S. H., Jang, C. G., Lee, J. H., Kim, H. C., & Nah, S. Y. (2012). Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. Journal of Alzheimer's Disease : JAD, 31(1), 207-23. https://doi.org/10.3233/JAD-2012-120439
Hwang SH, et al. Gintonin, a Ginseng-derived Lysophosphatidic Acid Receptor Ligand, Attenuates Alzheimer's Disease-related Neuropathies: Involvement of Non-amyloidogenic Processing. J Alzheimers Dis. 2012;31(1):207-23. PubMed PMID: 22543851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. AU - Hwang,Sung Hee, AU - Shin,Eun-Joo, AU - Shin,Tae-Joon, AU - Lee,Byung-Hwan, AU - Choi,Sun-Hye, AU - Kang,Jiyeon, AU - Kim,Hyeon-Joong, AU - Kwon,Seung-Hwan, AU - Jang,Choon-Gon, AU - Lee,Jun-Ho, AU - Kim,Hyoung-Chun, AU - Nah,Seung-Yeol, PY - 2012/5/1/entrez PY - 2012/5/1/pubmed PY - 2012/12/10/medline SP - 207 EP - 23 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 31 IS - 1 N2 - Ginseng extracts show cognition-enhancing effects in Alzheimer's disease (AD) patients. However, little is known about the active components and molecular mechanisms of how ginseng exerts its effects. Recently, we isolated a novel lysophosphatidic acid (LPA) receptor-activating ligand from ginseng, gintonin. AD is caused by amyloid-β protein (Aβ) accumulation. Aβ is derived from amyloid-β protein precursors (AβPPs) through the amyloidogenic pathway. In contrast, non-amyloidogenic pathways produce beneficial, soluble AβPPα (sAβPPα). Here, we describe our investigations of the effect of gintonin on sAβPPα release, Aβ formation, Swedish-AβPP transfection-mediated neurotoxicity in SH-SY5Y neuroblastoma cells, and Aβ-induced neuropathy in mice. Gintonin promoted sAβPPα release in a concentration- and time-dependent manner. Gintonin action was also blocked by the Ca2+ chelator BAPTA, α-secretase inhibitor TAPI-2, and protein-trafficking inhibitor brefeldin. Gintonin decreased Aβ1-42 release and attenuated Aβ1-40-induced cytotoxicity in SH-SY5Y cells. Gintonin also rescued Aβ1-40-induced cognitive dysfunction in mice. Moreover, in a transgenic mouse AD model, long-term oral administration of gintonin attenuated amyloid plaque deposition as well as short- and long-term memory impairment. In the present study, we demonstrated that gintonin mediated the promotion of non-amyloidogenic processing to stimulate sAβPPα release to restore brain function in mice with AD. Gintonin could be a useful agent for AD prevention or therapy. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/22543851/Gintonin_a_ginseng_derived_lysophosphatidic_acid_receptor_ligand_attenuates_Alzheimer's_disease_related_neuropathies:_involvement_of_non_amyloidogenic_processing_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2012-120439 DB - PRIME DP - Unbound Medicine ER -