5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders.
There is evidence of an association between depression and anxiety and cardio- cerebro-vascular conditions, but the mechanisms of this association are unknown. Here we review a possible role for the 5-lipoxygenase (5-LOX) pathway. 5-LOX is an enzyme that, in association with 5-LOX-activating protein (FLAP), leads to the synthesis of leukotrienes from omega-6 arachidonic acid. Production of active leukotrienes can be reduced by dietary omega-3 fatty acids, which also are beneficial in cardiac and psychiatric (e.g., depression) pathologies. Human 5-LOX and FLAP gene polymorphisms are a risk factor in atherosclerosis and cardio-cerebro-vascular pathologies; an overactive 5-LOX pathway is found in these diseases. Studies with 5-LOX-deficient transgenic mice suggest that 5-LOX activity may contribute to anxiety- and depression-like behaviors. Future research should characterize the role of the 5-LOX pathway in comorbid cardio-cerebro-vascular and psychiatric disorders and in the therapeutic actions of dietary omega-3 fatty acids.
Manev
Radmila
R
The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Manev
Hari
H
D058927:5-Lipoxygenase-Activating Proteins; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000502:physiology*; D001161:Arteriosclerosis / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D001523:Mental Disorders / Q000201:enzymology* / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D011110:Polymorphism, Genetic / Q000235:genetics; D020521:Stroke / Q000503:physiopathology
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; C548593:Alox5ap protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D001094:Arachidonate 5-Lipoxygenase