Numerous reports have indicated that patients suffering from inflammatory d
iseases (e.g., arthritis) who take anti-inflammatory medication have a redu
ced 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 gastrointe
stinal system from the resultant reduced cytoprotection, selective COX-2 in
hibitors are being investigated and tested clinically as potentially better
therapeutics for AD patients. However, such drugs may also trigger unwante
d effects; for example, the COX-2 inhibitors, which reduce the production o
f one type of eicosanoids, the prostaglandins, may increase the production
of other eicosanoids; i.e., the leukotriene B-4 (LTB4), which is one of the
most potent endogenous chemotactic/inflammatory factors. LTB4 production i
s initiated by the enzyme 5-lipoxygenase (5-LOX). The expression of the 5-L
OX 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 in
vestigated. We propose that the 5-LOX inflammatory cascade may take part in
the process of aging-associated neurodegenerative diseases, and we point t
o the role of 5-LOX in neurodegeneration and discuss its relevance for anti
-inflammatory therapy of AD.