title: Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway.
abstract: Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases including Alzheimer's disease (AD), in which dysregulation of double-stranded RNA-dependent protein kinase (PKR)-like ER-resident kinase (PERK) is considered to play a critical role. Allicin, a garlic extract, has been demonstrated a protective role in AD model. The present study was designed to investigate the possible protective effect of allicin on ER stress-induced cognitive deficits and underlying mechanisms in rats. In this study, 72h of lateral ventricular infusion of tunicamycin (TM), an ER stress stimulator, induced significant cognitive deficits. TM increased tau phosphorylation, Aβ42 deposit, and oxidative stress, and reduced antioxidative enzymes activity in the hippocampus. TM moderately elevated the expression of PERK and its downstream substrate nuclear factor erythroid-derived 2-like 2 (Nrf2) in the hippocampus. All these impaired changes by TM were significantly improved by allicin pretreatment. Allicin markedly increased PERK and Nrf2 expression in the hippocampus. Thus, our data demonstrate the protective role of allicin in ER stress-related cognitive deficits, and suggest that PERK/Nrf2 antioxidative signaling pathway underlies the action mechanism.
authors.affiliation: Institute of Medicine, College of Medicine, Jishou University, Jishou City, Hunan Province 416000, China.
authors.forename: Yao-Feng
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: Institute of Medicine, College of Medicine, Jishou University, Jishou City, Hunan Province 416000, China; Aid Program from Science and Technology Innovative Research Team in Jishou University for Improving Drug-like Properties of Active Components from Medicinal Plants in Wulin Mountains, China. Electronic address: lxhsurgeon@163.com.
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Institute of Medicine, College of Medicine, Jishou University, Jishou City, Hunan Province 416000, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Yuan
authors.affiliation: Institute of Medicine, College of Medicine, Jishou University, Jishou City, Hunan Province 416000, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Institute of Medicine, College of Medicine, Jishou University, Jishou City, Hunan Province 416000, China.
authors.forename: Rong-Bo
authors.initials: RB
authors.lastname: Tian
authors.affiliation: Institute of Medicine, College of Medicine, Jishou University, Jishou City, Hunan Province 416000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Aid Program from Science and Technology Innovative Research Team in Jishou University for Improving Drug-like Properties of Active Components from Medicinal Plants in Wulin Mountains, China.
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004220:Disulfides; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013441:Sulfinic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D014415:Tunicamycin / Q000009:adverse effects; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D004220:Disulfides; D051267:NF-E2-Related Factor 2; D010446:Peptide Fragments; D013441:Sulfinic Acids; D014415:Tunicamycin; D019892:eIF-2 Kinase; D016875:tau Proteins; C495637:Nfe2l2 protein, rat; C075222:amyloid beta-protein (1-42); C006452:allicin
keywords: Allicin; Alzheimer's disease; Endoplasmic reticulum stress; Nrf2; PERK