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RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer's disease animal model.
FASEB J. 2009 Aug; 23(8):2639-49.FJ

Abstract

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor, and amyloid beta peptide (Abeta) is one of the ligands for RAGE. Because RAGE is a transporter of Abeta from the blood to the brain, RAGE is believed to play an important role in Alzheimer's disease (AD) pathogenesis. In the present study, the role of RAGE in Abeta production was examined in the brain tissue of an AD animal model, Tg2576 mice, as well as cultured cells. Because beta-site APP-cleaving enzyme 1 (BACE1), an essential protease for Abeta production, is up-regulated in cells overexpressing RAGE and in RAGE-injected brains of Tg2576 mice, the molecular mechanisms underlying RAGE, BACE1 expression, and Abeta production were examined. Because RAGE stimulates intracellular calcium, nuclear factor of activated T-cells 1 (NFAT1) was examined. NFAT1 was activated following RAGE-induced BACE1 expression followed by Abeta generation. Injection of soluble RAGE (sRAGE), which acts as a competitor with full-length RAGE (fRAGE), into aged Tg2576 mouse brains reduced the levels of plaques, Abeta, BACE1, and the active form of NFAT1 compared with fRAGE-injected Tg2576 mice. Taken together, RAGE stimulates functional BACE1 expression through NFAT1 activation, resulting in more Abeta production and deposition in the brain.

Authors+Show Affiliations

Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 28 Yungun-dong, Jongro-gu, Seoul, 110-799, Korea.No 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

19332646

Citation

Cho, H J., et al. "RAGE Regulates BACE1 and Abeta Generation Via NFAT1 Activation in Alzheimer's Disease Animal Model." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 23, no. 8, 2009, pp. 2639-49.
Cho HJ, Son SM, Jin SM, et al. RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer's disease animal model. FASEB J. 2009;23(8):2639-49.
Cho, H. J., Son, S. M., Jin, S. M., Hong, H. S., Shin, D. H., Kim, S. J., Huh, K., & Mook-Jung, I. (2009). RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer's disease animal model. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 23(8), 2639-49. https://doi.org/10.1096/fj.08-126383
Cho HJ, et al. RAGE Regulates BACE1 and Abeta Generation Via NFAT1 Activation in Alzheimer's Disease Animal Model. FASEB J. 2009;23(8):2639-49. PubMed PMID: 19332646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer's disease animal model. AU - Cho,H J, AU - Son,S M, AU - Jin,S M, AU - Hong,H S, AU - Shin,D H, AU - Kim,S J, AU - Huh,K, AU - Mook-Jung,I, Y1 - 2009/03/30/ PY - 2009/4/1/entrez PY - 2009/4/1/pubmed PY - 2009/8/19/medline SP - 2639 EP - 49 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 23 IS - 8 N2 - The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor, and amyloid beta peptide (Abeta) is one of the ligands for RAGE. Because RAGE is a transporter of Abeta from the blood to the brain, RAGE is believed to play an important role in Alzheimer's disease (AD) pathogenesis. In the present study, the role of RAGE in Abeta production was examined in the brain tissue of an AD animal model, Tg2576 mice, as well as cultured cells. Because beta-site APP-cleaving enzyme 1 (BACE1), an essential protease for Abeta production, is up-regulated in cells overexpressing RAGE and in RAGE-injected brains of Tg2576 mice, the molecular mechanisms underlying RAGE, BACE1 expression, and Abeta production were examined. Because RAGE stimulates intracellular calcium, nuclear factor of activated T-cells 1 (NFAT1) was examined. NFAT1 was activated following RAGE-induced BACE1 expression followed by Abeta generation. Injection of soluble RAGE (sRAGE), which acts as a competitor with full-length RAGE (fRAGE), into aged Tg2576 mouse brains reduced the levels of plaques, Abeta, BACE1, and the active form of NFAT1 compared with fRAGE-injected Tg2576 mice. Taken together, RAGE stimulates functional BACE1 expression through NFAT1 activation, resulting in more Abeta production and deposition in the brain. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/19332646/RAGE_regulates_BACE1_and_Abeta_generation_via_NFAT1_activation_in_Alzheimer's_disease_animal_model_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.08-126383?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -