title: Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Aβ)-induced damage in vitro and in vivo.
abstract: In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Aβ)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Aβ25-35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Aβ1-40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Aβ peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer's disease.
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; School of Ocean, Shandong University, Weihai 264209, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Neurosurgery, Weihai Municipal Hospital, Weihai 264009, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Ocean, Shandong University, Weihai 264209, China.
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: F
authors.initials: F
authors.lastname: Yin
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: A
authors.initials: A
authors.lastname: Zong
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address: fswang@sdu.edu.cn.
authors.forename: F
authors.initials: F
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000150:complications; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C078592:amyloid beta-protein (1-40); D002809:Chondroitin Sulfates; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D053148:Caspase 3; D002118:Calcium
keywords: Alzheimer’s disease (AD); amyloid beta protein (Aβ); low molecular weight chondroitin sulfate (LMWCS); neuroprotection