title: Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-β C-terminal peptides.
abstract: Amyloid-β (Aβ) deposition and oxidative stress observed in the brains of patients with Alzheimer's disease (AD) are important targets for therapeutic intervention. In this study, we conjugated the antioxidants caffeic acid (CA) and dihydrocaffeic acid (DHCA) to Aβ1-42C-terminal motifs (Aβx-42: x=38, 40) to synthesize CA-Aβx-42and DHCA-Aβx-42, respectively. Among the compounds, CA-Aβ38-42exhibited potent inhibitory activity against Aβ1-42aggregation and scavenged Aβ1-42-induced intracellular oxidative stress. Moreover, CA-Aβ38-42significantly protected human neuroblastoma SH-SY5Y cells against Aβ1-42-induced cytotoxicity, with an IC50of 4μM. These results suggest that CA-Aβ38-42might be a potential lead for the treatment of AD.
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan; School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Takuya
authors: T
authors: Arai
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors: Akiko
authors: A
authors: Ohno
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Kazunori
authors: K
authors: Mori
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Hiroshi
authors: H
authors: Kuwata
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Mirei
authors: M
authors: Mizuno
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Kohei
authors: K
authors: Imai
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Shuntaro
authors: S
authors: Hara
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Motoko
authors: M
authors: Shibanuma
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors: Masaaki
authors: M
authors: Kurihara
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Naoki
authors: N
authors: Miyata
authors: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Hidehiko
authors: H
authors: Nakagawa
authors: School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: fukuhara@pharm.showa-u.ac.jp.
authors: Kiyoshi
authors: K
authors: Fukuhara
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D066329:Protein Aggregates / Q000187:drug effects*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002109:Caffeic Acids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); C000995:3,4-dihydroxyphenylpropionic acid; C040048:caffeic acid
keywords: Aggregation inhibitor; Alzheimer’s disease; Amyloid-β; Antioxidative activity; Caffeic acid; Cytotoxicity