Tenuigenin treatment decreases secretion of the Alzheimer’s disease amyloid β-protein in cultured cells

• Published in: Neuroscience letters Vol. 367; no. 1; pp. 123 - 128
• Main Authors: Jia, Hongxiao, Jiang, Yong, Ruan, Yan, Zhang, Yanbo, Ma, Xin, Zhang, Jizhi, Beyreuther, Konrad, Tu, Penfei, Zhang, Dai
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 26.08.2004; Elsevier
• Subjects: Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases; Amyloid β-protein (Aβ); Analysis of Variance; Aspartic Acid Endopeptidases - metabolism; Biological and medical sciences; Blotting, Western - methods; C-terminal 99 amino acids of APP (C99); Cell Line, Tumor; Cell Survival - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - pharmacology; Endopeptidases; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Humans; Immunoprecipitation - methods; L-Lactate Dehydrogenase; Medical sciences; Neuroblastoma; Neurology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Tenuiginin; Tetrazolium Salts; Thiazoles; Transfection - methods; Vertebrates: nervous system and sense organs; β-Secretase; Amyloid β-protein (Aβ); β-Secretase; C-terminal 99 amino acids of APP (C99); Tenuiginin; Nervous system diseases; Alzheimer disease; Secretion; In vitro; Cerebral disorder; β Amyloid protein; Aminoacid; Central nervous system disease; β-secretase; Degenerative disease
• DOI: 10.1016/j.neulet.2004.05.093
• ISSN: 0304-3940

Amyloid β-protein (Aβ) is a pivotal pathological factor in Alzheimer’s disease (AD). Tenuigenin, extracted from the Chinese herb Polygala tenuifolia, seems to ameliorate the reduction in cholinergic function on rat models induced by Aβ. To examine this therapeutic effect, we tested whether Tenuigenin could inhibit secretion of Aβ in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y APP695) and the C-terminal 99 amino acid residues of APP plus the signal peptide (SH-SY5Y SPA4CT). Tenuigenin inhibited the secretion of Aβ and the C-terminal 99 amino acids of APP (C99) in SH-SY5Y APP695 cells, but did not change the Aβ and C99 levels in SH-SY5Y SPA4CT cells. Fluorescence Resonance Energy Transfer (FRET) assays showed that Tenuigenin inhibited the proteolytic activities of BACE1 (β-secretase) on its substrate in vitro. In addition, Tenuigenin did not demonstrate any cytotoxic effects, nor did it affect APP mRNA expression, holoAPP synthesis or sAPPα secretion. Our data suggest that Tenuigenin can inhibit the secretion of Aβ in SH-SY5Y APP 695 cells via BACE1 inhibition. Taken together, these results suggest that Tenuigenin may be worthy of future study as an anti-AD drug.