Amyloid-β-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans

被引:307
作者
Wu, Yanjue
Wu, Zhixin
Butko, Peter
Christen, Yves
Lambert, Mary P.
Klein, William L.
Link, Christopher D.
Luo, Yuan [1 ]
机构
[1] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA
[2] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA
[3] Univ So Mississippi, Dept Chem & Biochem, Hattiesburg, MS 39406 USA
[4] Ispen, F-75016 Paris, France
[5] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA
[6] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA
关键词
A beta peptide; Alzheimer's disease; behavior; mutant; phenotype; serotonin;
D O I
10.1523/JNEUROSCI.3448-06.2006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Amyloid-beta (A beta) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that the standardized Ginkgo biloba extract EGb 761, commonly used to enhance memory and by AD patients for dementia, inhibits A beta-induced apoptosis in neuroblastoma cells. In this study, we use EGb 761 and its single constituents to associate A beta species with A beta-induced pathological behaviors in a model organism, Caenorhabditis elegans. We report that EGb 761 and one of its components, ginkgolide A, alleviates A beta-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans. We also show that EGb 761 inhibits A beta oligomerization and A beta deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress A beta-induced paralysis because the antioxidant L-ascorbic acid reduced intracellular levels of hydrogen peroxide to the same extent as EGb 761, but was not nearly as effective in suppressing paralysis in the transgenic C. elegans. These findings suggest that (1) EGb 761 suppresses A beta-related pathological behaviors, (2) the protection against A beta toxicity by EGb761 is mediated primarily by modulating A beta oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.
引用
收藏
页码:13102 / 13113
页数:12
相关论文
共 70 条
[21]   Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABAA receptors [J].
Ivic, L ;
Sands, TTJ ;
Fishkin, N ;
Nakanishi, K ;
Kriegstein, AR ;
Stromgaard, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (49) :49279-49285
[22]   Isolation of ginkgolides A, B, C, J and bilobalide from G-biloba extracts [J].
Jaracz, S ;
Malik, S ;
Nakanishi, K .
PHYTOCHEMISTRY, 2004, 65 (21) :2897-2902
[23]   Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis [J].
Kayed, R ;
Head, E ;
Thompson, JL ;
McIntire, TM ;
Milton, SC ;
Cotman, CW ;
Glabe, CG .
SCIENCE, 2003, 300 (5618) :486-489
[24]   Intracellular amyloid-β1-42, but not extracellular soluble amyloid-β peptides, induces neuronal apoptosis [J].
Kienlen-Campard, P ;
Miolet, S ;
Tasiaux, B ;
Octave, JN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (18) :15666-15670
[25]   Inhibition of hippocampal UP by ginkgolide B is mediated by its blocking action on PAF rather than glycine receptors [J].
Kondratskaya, EL ;
Pankratov, YV ;
Lalo, UV ;
Chatterjee, SS ;
Krishtal, OA .
NEUROCHEMISTRY INTERNATIONAL, 2004, 44 (03) :171-177
[26]   Vaccination with soluble Aβ oligomers generates toxicity-neutralizing antibodies [J].
Lambert, MP ;
Viola, KL ;
Chromy, BA ;
Chang, L ;
Morgan, TE ;
Yu, JX ;
Venton, DL ;
Krafft, GA ;
Finch, CE ;
Klein, WL .
JOURNAL OF NEUROCHEMISTRY, 2001, 79 (03) :595-605
[27]   Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins [J].
Lambert, MP ;
Barlow, AK ;
Chromy, BA ;
Edwards, C ;
Freed, R ;
Liosatos, M ;
Morgan, TE ;
Rozovsky, I ;
Trommer, B ;
Viola, KL ;
Wals, P ;
Zhang, C ;
Finch, CE ;
Krafft, GA ;
Klein, WL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6448-6453
[28]  
LAMBERT MP, 2006, IN PRESS J NEUROCHEM
[29]  
Le Bars PL, 2003, PHARMACOPSYCHIATRY, V36, pS44
[30]   A 26-week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb 761® in dementia [J].
Le Bars, PL ;
Kieser, M ;
Itil, K .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2000, 11 (04) :230-237