title: Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there are few therapeutic regimens that influence the underlying pathogenic phenotypes. However, of the currently available therapies, exercise training is considered to be one of the best candidates for amelioration of the pathological phenotypes of AD. Therefore, we directly investigated exercise training to determine whether it was able to ameliorate the molecular pathogenic phenotypes in the brain using a neuron-specific enolase (NSE)/Swedish mutation of amyloid precursor protein (APPsw) transgenic (Tg) mice as a novel AD model. To accomplish this, Non-Tg and NSE/ APPsw Tg mice were subjected to exercise on a treadmill for 16 weeks, after which their brains were evaluated to determine whether any changes in the pathological phenotype-related factors had occurred. The results indicated (i) that amyloid beta-42 (Abeta-42) peptides were significantly decreased in the NSE/APPsw Tg mice following exercise training; (ii) that exercise training inhibited the apoptotic biochemical cascades, including cytochrome c, caspase-9, caspase-3 and Bax; (iii) that the glucose transporter-1 (GLUT-1) and brain-derived neurotrophic factor (BDNF) proteins induced by exercise training protected the neurons from injury by inducing the concomitant expression of genes that encode proteins such as superoxide dismutase-1 (SOD-1), catalase and Bcl-2, which suppress oxidative stress and excitotoxic injury; (iv) that heat-shock protein-70 (HSP-70) and glucose-regulated protein-78 (GRP-78) were significantly increased in the exercise (EXE) group when compared to the sedentary (SED) group, and that these proteins may benefit the brain by making it more resistant to stress-induced neuron cell damage; (v) and that exercise training contributed to the restoration of normal levels of serum total cholesterol, insulin and glucose. Taken together, these results suggest that exercise training represents a practical therapeutic strategy for human subjects suffering from AD. Moreover, this training has the potential for use in new therapeutic strategies for the treatment of other chronic disease including diabetes, cardiovascular and Parkinson's disease.
authors.affiliation: Exercise Biochemistry Laboratory, Korea National Sport University, Seoul 138-763, Korea.
authors.forename: Hyun Seob
authors.initials: HS
authors.lastname: Um
authors.forename: Eun Bum
authors.initials: EB
authors.lastname: Kang
authors.forename: Yea Hyun
authors.initials: YH
authors.lastname: Leem
authors.forename: In Ho
authors.initials: IH
authors.lastname: Cho
authors.forename: Chun Ho
authors.initials: CH
authors.lastname: Yang
authors.forename: Kab Ryong
authors.initials: KR
authors.lastname: Chae
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
authors.forename: Joon Yong
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000201:enzymology / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D000091342:Endoplasmic Reticulum Chaperone BiP; D051272:Glucose Transporter Type 1; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D013482:Superoxide Dismutase; D020169:Caspases; D010751:Phosphopyruvate Hydratase