title: Thiacremonone Potentiates Anti-Oxidant Effects to Improve Memory Dysfunction in an APP/PS1 Transgenic Mice Model.
abstract: Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) peptide. Evidence suggests that amyloid accumulation can be caused by oxidative stress and inflammatory responses. In this study, we examined neuroprotective effects of thiacremonone, an anti-oxidant and anti-inflammatory compound isolated from garlic. Treatment of thiacremonone significantly attenuated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) double-mutant transgenic mice. In addition, activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) pathways in the brain was potently inhibited by thiacremonone. We also observed that thiacremonone significantly inhibited activation of NF-κB and ERK pathways induced by H2O2 and Aβ1-42 in embryonic neuronal cells. Furthermore, thiacremonone augmented peroxiredoxin 6 (PRDX6) expression in vivo and in vitro associated with reduced oxidative stress of macromolecules such as protein and lipids. This study indicates that thiacremonone might exert memory improvement via stimulating anti-oxidant system. These multiple properties could attenuate Aβ accumulation and oxidative stress in Alzheimer's brains. Thus, these results suggest that thiacremonone might be useful to intervene development or progression of neurodegeneration in AD.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: JaeRyun
authors.initials: J
authors.lastname: Hwang
authors.affiliation: College of Agriculture, Life and Environments Sciences, Chungbuk National University, 12, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: Heon-Sang
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: Jea-Kyung
authors.initials: JK
authors.lastname: Jung
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea. jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D054465:Peroxiredoxin VI / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D016328:NF-kappa B; D053764:Presenilin-1; D013876:Thiophenes; C580804:presenilin 1, mouse; C524083:thiacremonone; D004247:DNA; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D053829:Amyloid Precursor Protein Secretases; D005978:Glutathione
keywords: Alzheimer’s disease; Amyloid-beta; Oxidative stress; Peroxiredoxin 6; Thiacremonone