title: Protective Effects of Fucoidan on Aβ25-35 and d-Gal-Induced Neurotoxicity in PC12 Cells and d-Gal-Induced Cognitive Dysfunction in Mice.
abstract: Alzheimer's disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells from apoptosis induced by a combination of beta-amyloid 25-35 (Aβ25-35) and d-galactose (d-Gal), and improves learning and memory impairment in AD model mice. The results indicated that fucoidan could inhibit the release of cytochrome c from the mitochondria to cytosol and activation of caspases, and increase the expression of apoptosis inhibitor proteins (IAPs), including livin and X-linked IAP (XIAP) in PC12 cells damaged by Aβ25-35 and d-Gal-induction. Fucoidan reversed the decreased activity of acetylcholine (ACh) and choline acetyl transferase (ChAT), as well as the increased activity of acetylcholine esterase (AChE), in AD model mice induced by infusion of d-Gal. Furthermore, fucoidan improved antioxidant activity in vitro and in vivo by activation of superoxide dismutase (SOD) and glutathione (GSH). These results suggested that fucoidan could protect PC12 cells from apoptosis and ameliorate the learning and memory impairment in AD model mice, which appeared to be due to regulating the cholinergic system, reducing oxidative stress, and inhibiting the caspase-dependent apoptosis pathway.
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. weihengyun@126.com.
authors.forename: Hengyun
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. 18641548759@163.com.
authors.forename: Zixiang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: College of Integrative Medicine, Dalian Medical University, Dalian 116044, China. zzllpp311@163.com.
authors.forename: Luping
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. biot_zhangcl@sina.com.
authors.forename: Cuili
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. harryblood1989@126.com.
authors.forename: Zundong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. yangyazong123@126.com.
authors.forename: Yazong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. thm0529@126.com.
authors.forename: Hongming
authors.initials: H
authors.lastname: Teng
authors.affiliation: College of Life Sciences, Liaoning Normal University, Dalian 116081, China. houlin01@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. yinyulingdl@dlmedu.edu.cn.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. zouxiangyang@126.com.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zou
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005690:Galactose / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011134:Polysaccharides; C074636:amyloid beta-protein (25-35); C007789:fucoidan; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase; D005978:Glutathione; D000109:Acetylcholine; D005690:Galactose
keywords: Alzheimer’s disease; amyloid-β peptide; apoptosis; fucoidan; neuroprotection