Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-β aggregation

被引:136
作者
Thomas, T [1 ]
Nadackal, TG [1 ]
Thomas, K [1 ]
机构
[1] Woodlands Med Ctr & Endron Therapeut, Oldsmar, FL 34677 USA
关键词
Alzheimer's disease; amyloid-beta; amyloid aggregation; amyloid plaque; aspirin; COX-2; inhibitors; inflammation; neurotoxicity; NSAIDs;
D O I
10.1097/00001756-200110290-00024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The neurotoxic and proinflammatory actions of the Alzheimer peptide amyloid-beta (A beta) are dependent on its aggregation and beta -sheet conformation. Chronic use of non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin for arthritis decreases the risk of developing Alzheimer's disease (AD) by unknown mechanisms. We report that these drugs inhibit human A beta aggregation in vitro and reverse the beta -sheet conformation of preformed fibrils at clinically relevant doses. Aspirin prevented enhanced A beta aggregation by aluminum, an environmental risk factor for AD. This anti-aggregatory effect was restricted to NSAIDs and was not exhibited by other drugs used in AD therapy. NSAIDS may have a role in the prevention and treatment of AD, in addition to a number of age-related disorders such as arthritis, cardiovascular disease and cancer. NeuroReport 12:3263-3267 (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:3263 / 3267
页数:5
相关论文
共 30 条
  • [21] The genetics and molecular pathology of Alzheimer's disease - Roles of amyloid and the presenilins
    Selkoe, DJ
    [J]. NEUROLOGIC CLINICS, 2000, 18 (04) : 903 - +
  • [22] SOLVENT EFFECTS ON SELF-ASSEMBLY OF BETA-AMYLOID PEPTIDE
    SHEN, CL
    MURPHY, RM
    [J]. BIOPHYSICAL JOURNAL, 1995, 69 (02) : 640 - 651
  • [23] β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis:: Implications for Alzheimer's therapy
    Soto, C
    Sigurdsson, EM
    Morelli, L
    Kumar, RA
    Castano, EM
    Frangione, B
    [J]. NATURE MEDICINE, 1998, 4 (07) : 822 - 826
  • [24] beta-Amyloid-mediated vasoactivity and vascular endothelial damage
    Thomas, T
    Thomas, G
    McLendon, C
    Sutton, T
    Mullan, M
    [J]. NATURE, 1996, 380 (6570) : 168 - 171
  • [25] Estrogen and raloxifene activities on amyloid-β-induced inflammatory reaction
    Thomas, T
    Bryant, M
    Clark, L
    Garces, A
    Rhodin, J
    [J]. MICROVASCULAR RESEARCH, 2001, 61 (01) : 28 - 39
  • [26] Monoamine oxidase-B inhibitors in the treatment of Alzheimers disease
    Thomas, T
    [J]. NEUROBIOLOGY OF AGING, 2000, 21 (02) : 343 - 348
  • [27] Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin - Its possible function as a hydroxyl radical scavenger
    Tomiyama, T
    Shoji, A
    Kataoka, K
    Suwa, Y
    Asano, S
    Kaneko, H
    Endo, N
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (12) : 6839 - 6844
  • [28] In vivo antithrombotic effects of a nitric oxide-releasing aspirin derivative, NCX-4016
    Wallace, JL
    Muscara, MN
    McKnight, W
    Dicay, M
    Del Soldato, P
    Cirino, G
    [J]. THROMBOSIS RESEARCH, 1999, 93 (01) : 43 - 50
  • [29] Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs
    Wolfe, MM
    Lichtenstein, DR
    Singh, G
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (24) : 1888 - 1899
  • [30] YANG JT, 1986, METHOD ENZYMOL, V130, P208