The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
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New Anti-inflammatory Treatment Strategy in Alzheimer’s Disease
Kiminobu SugayaTolga UzVinod KumarHari Manev
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2000 Volume 82 Issue 2 Pages 85-94

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Abstract

Numerous reports have indicated that patients suffering from inflammatory diseases(e.g., arthritis)who take anti-inflammatory medication have a reduced risk of developing Alzheimer’s disease(AD).Thus, the first generation of anti-inflammatory cyclooxygenase(COX)inhibitors, such as aspirin and indomethacin, have been tested as potential therapeutics in AD.Because the inhibition of COX-1 is also known to cause tissue damage in the gastrointestinal system from the resultant reduced cytoprotection, selective COX-2 inhibitors are being investigated and tested clinically as potentially better therapeutics for AD patients.However, such drugs may also trigger unwanted effects;for example, the COX-2 inhibitors, which reduce the production of one type of eicosanoids, the prostaglandins, may increase the production of other eicosanoids;i.e., the leukotriene B4(LTB4), which is one of the most potent endogenous chemotactic/inflammatory factors.LTB4 production is initiated by the enzyme 5-lipoxygenase(5-LOX).The expression of the 5-LOX gene is upregulated during neurodegeneration and with aging.In spite of the fact that 5-LOX and leukotrienes are major players in the inflammation cascade, their role in AD pathobiology/therapy has not been extensively investigated.We propose that the 5-LOX inflammatory cascade may take part in the process of aging-associated neurodegenerative diseases, and we point to the role of 5-LOX in neurodegeneration and discuss its relevance for anti-inflammatory therapy of AD.

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© The Japanese Pharmacological Society 2000
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