Putative role of neuronal 5-lipoxygenase in an aging brain

Aging is associated with increased incidence and/or severity of neurodegene rative pathologies. Oxygen-mediated events are being considered as possible mechanisms responsible for the increasing neuronal vulnerability. Lipoxyge nases are enzymes that, as cyclooxygenases (COX), can insert oxygen into th e molecule of arachidonic acid and thereby synthesize inflammatory eicosano ids: leukotrienes [due to 5-lipoxygenase (5-LOX) activity] and prostaglandi ns (via COX activity), It appears that 5-LOX is expressed in central nervou s system neurons and may participate in neurodegeneration. 5-LOX-triggered cell death may be initiated by the enzymatic activity of 5-LOX but could al so occur via the nonenzymatic actions of the 5-LOX protein; new data point to the possibility that 5-LOX protein exerts actions such as interaction wi th tyrosine kinase receptors, cytoskeletal proteins, and the nucleus. The e xpression of neuronal 5-LOX is susceptible to hormonal regulation, presumab ly due to the presence of hormone-responsive elements in the structure of t he 5-LOX gene promoter. The expression of the 5-LOX gene and the activity o f the 5-LOX pathway are increased in elderly subjects. One possible mechani sm of such 5-LOX up-regulation implies the contribution of aging-associated hormonal changes: relative melatonin deficiency and/or hyperglucocorticoid emia. Thus, the 5-LOX pathway could become a promising target of neuroprote ctive therapies for the aging brain.