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

被引：137

作者：

Thomas, T ^{[1
]}

Nadackal, TG ^{[1
]}

Thomas, K ^{[1
]}

机构：

[1] Woodlands Med Ctr & Endron Therapeut, Oldsmar, FL 34677 USA

来源：

NEUROREPORT | 2001年 / 12卷 / 15期

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

页码：3263 / 3267

页数：5

共 30 条

[11] Targeting small Aβ oligomers:: the solution to an Alzheimer's disease conundrum? [J].

Klein, WL ;

Krafft, GA ;

Finch, CE .

TRENDS IN NEUROSCIENCES, 2001, 24 (04) :219-224

[12] Pharmacological drug treatment of Alzheimer disease: The cholinergic hypothesis revisited [J].

Ladner, CJ ;

Lee, JM .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1998, 57 (08) :719-731

[13] THE INHIBITION OF SUGAR-INDUCED STRUCTURAL ALTERATIONS IN COLLAGEN BY ASPIRIN AND OTHER COMPOUNDS [J].

MALIK, NS ;

MEEK, KM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 199 (02) :683-686

[14] ALUMINUM, IRON, AND ZINC IONS PROMOTE AGGREGATION OF PHYSIOLOGICAL CONCENTRATIONS OF BETA-AMYLOID PEPTIDE [J].

MANTYH, PW ;

GHILARDI, JR ;

ROGERS, S ;

DEMASTER, E ;

ALLEN, CJ ;

STIMSON, ER ;

MAGGIO, JE .

JOURNAL OF NEUROCHEMISTRY, 1993, 61 (03) :1171-1174

[15] The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases [J].

McGeer, PL ;

McGeer, EG .

BRAIN RESEARCH REVIEWS, 1995, 21 (02) :195-218

[16] Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline [J].

Näslund, J ;

Haroutunian, V ;

Mohs, R ;

Davis, KL ;

Davies, P ;

Greengard, P ;

Buxbaum, JD .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2000, 283 (12) :1571-1577

[17]

PAULUS HE, 1997, PRIMER RHEUMATIC DIS, P422

[18] STRUCTURE-ACTIVITY ANALYSES OF BETA-AMYLOID PEPTIDES - CONTRIBUTIONS OF THE BETA-25-35 REGION TO AGGREGATION AND NEUROTOXICITY [J].

PIKE, CJ ;

WALENCEWICZWASSERMAN, AJ ;

KOSMOSKI, J ;

CRIBBS, DH ;

GLABE, CG ;

COTMAN, CW .

JOURNAL OF NEUROCHEMISTRY, 1995, 64 (01) :253-265

[19] CLINICAL-TRIAL OF INDOMETHACIN IN ALZHEIMERS-DISEASE [J].

ROGERS, J ;

KIRBY, LC ;

HEMPELMAN, SR ;

BERRY, DL ;

MCGEER, PL ;

KASZNIAK, AW ;

ZALINSKI, J ;

COFIELD, M ;

MANSUKHANI, L ;

WILLSON, P ;

KOGAN, F .

NEUROLOGY, 1993, 43 (08) :1609-1611

[20] Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans [J].

Scott, MR ;

Will, R ;

Ironside, J ;

Nguyen, HOB ;

Tremblay, P ;

DeArmond, SJ ;

Prusiner, SB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15137-15142

← 1 2 3 →