Putative role of neuronal 5‐lipoxygenase in an aging brain

Abstract

Aging is associated with increased incidence and/or severity of neurodegenerative pathologies. Oxygen‐mediated events are being considered as possible mechanisms responsible for the increasing neuronal vulnerability. Lipoxygenases are enzymes that, as cyclooxygenases (COX), can insert oxygen into the molecule of arachidonic acid and thereby synthesize inflammatory eicosanoids: leukotrienes [due to 5‐lipoxygenase (5‐LOX) activity] and prostaglandins (via COX activity). It appears that 5‐LOX is expressed in central nervous system neurons and may participate in neurodegeneration. 5‐LOX‐triggered cell death may be initiated by the enzymatic activity of 5‐LOX but could also 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 with tyrosine kinase receptors, cytoskeletal proteins, and the nucleus. The expression of neuronal 5‐LOX is susceptible to hormonal regulation, presumably due to the presence of hormone‐responsive elements in the structure of the 5‐LOX gene promoter. The expression of the 5‐LOX gene and the activity of the 5‐LOX pathway are increased in elderly subjects. One possible mechanism of such 5‐LOX up‐regulation implies the contribution of aging‐associated hormonal changes: relative melatonin deficiency and/or hyper‐glucocorticoidemia. Thus, the 5‐LOX pathway could become a promising target of neuroprotective therapies for the aging brain.—Manev, H., Uz, T., Sugaya, K., Qu, T. Putative role of neuronal 5‐lipoxygenase in an aging brain. FASEB J. 14, 1464–1469 (2000)

Diet-induced effects on neuronal and glial elements in the middle-aged rat hippocampus

“…58 There is a marked loss of 5-LOX immunoreactive cells in the pyramidal layer of the CA1 (Figs 3 and 4I-L) particularly in the LARD group which is consistent with our findings for the MAP2 antibody discussed above. Equally notable is the results for HSO fed animals which exhibit a loss of 5-LOX expression throughout the hippocampus.…”

Excessive Leukotriene B4 in Nucleus Tractus Solitarii Is Prohypertensive in Spontaneously Hypertensive Rats

“…5-lipoxygenase is a lipoxygenase present in the central nervous system 24 . Its up regulation in the NTS of the SHR together with the down regulation of LTB4-12-HD, the enzyme that causes dehydrogenation of LTB4 to 12-oxo-LTB4, could both cause the elevated levels of LTB4 that we found.…”

Damaging effects of a high-fat diet to the brain and cognition: A review of proposed mechanisms

“…45,86,87 Levels of cyclooxygenase, lipoxygenase, prostanoids, and eicosanoids, all components of inflammatory pathways, have also been shown to be elevated in the brain with aging. 45,88,89 Furthermore, it has been shown that there is a progressive deterioration of the immune response with increased aging, including time to build a response, level of activation, and speed in which the response is ended. 90–92 This altered immune response occurs in the periphery as well as in the brain.…”