Devaraj S, Jialal I.
Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase.
Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1125-33.
PubMed.
Inflammation, free radicals, and cytokines are involved in a vascular cascade producing the transformation of macrophages into foam cells between the endothelial cell layer and the basement membrane of a blood vessel leading to formation of an atherosclerotic plaque. Similarly, inflammation, free radicals, and cytokines are opined to be involved in beta-amyloid plaque formation, but probably mediated by microglia--a cell type exhibiting capabilities similar to those of monocytes—leading to the deposition of a pathologically produced peptide. Alternatively, beta-amyloid deposited in blood vessels is located differently; it can be either interdigitated with the basement membrane or in the muscle layer.
Devaraj and Jialal have convincingly demonstrated that Vitamin E (alpha-tocopherol) reduces interleukin-1-beta release from monocytes by inhibition of 5-lipoxygenase (5-LO), thereby attenuating a proposed inflammatory first step in atherosclerotic lesion formation. There is emerging data suggesting that critically stenotic coronary atherosclerosis can precipitate the pre-mature incidence of Alzheimer-like neuropathology in the form of beta-amyloid-containing senile plaques. There is also considerable evidence that there is a vascular component (compromise) in Alzheimer's disease. It can easily be suggested that the process inhibited by Vitamin E at the level of the coronary artery may also be effective at the level of the cerebral vasculature in Alzheimer's disease.
It is of note that we have recently identified and reported vascular inflammation in Alzheimer's disease brain. We would suggest that vascular inflammation and compromise could contribute to the progressive formation of characteristic neuropathology in Alzheimer's disease, and in turn, the eventual clinical manifestations of the disorder. Therefore, targeting 5-LO as a point of therapeutic intervention in Alzheimer's disease at the cerebrovascular level could possibly disrupt senile plaque formation in the underlying brain tissue before it starts.
As 5-LO is a membrane translocated enzyme and Vitamin E is known to reduce membrane fluidity, it should also be noted that the mechanism of inhibition could be physical rather than chemical. The decrease in membrane fluidity caused by the Vit E may not allow effective 5-LO translocation.
References:
Devaraj S, Jialal I.
Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase.
Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1125-33.
PubMed.
Comments
Deceased, 2013
Inflammation, free radicals, and cytokines are involved in a vascular cascade producing the transformation of macrophages into foam cells between the endothelial cell layer and the basement membrane of a blood vessel leading to formation of an atherosclerotic plaque. Similarly, inflammation, free radicals, and cytokines are opined to be involved in beta-amyloid plaque formation, but probably mediated by microglia--a cell type exhibiting capabilities similar to those of monocytes—leading to the deposition of a pathologically produced peptide. Alternatively, beta-amyloid deposited in blood vessels is located differently; it can be either interdigitated with the basement membrane or in the muscle layer.
Devaraj and Jialal have convincingly demonstrated that Vitamin E (alpha-tocopherol) reduces interleukin-1-beta release from monocytes by inhibition of 5-lipoxygenase (5-LO), thereby attenuating a proposed inflammatory first step in atherosclerotic lesion formation. There is emerging data suggesting that critically stenotic coronary atherosclerosis can precipitate the pre-mature incidence of Alzheimer-like neuropathology in the form of beta-amyloid-containing senile plaques. There is also considerable evidence that there is a vascular component (compromise) in Alzheimer's disease. It can easily be suggested that the process inhibited by Vitamin E at the level of the coronary artery may also be effective at the level of the cerebral vasculature in Alzheimer's disease.
It is of note that we have recently identified and reported vascular inflammation in Alzheimer's disease brain. We would suggest that vascular inflammation and compromise could contribute to the progressive formation of characteristic neuropathology in Alzheimer's disease, and in turn, the eventual clinical manifestations of the disorder. Therefore, targeting 5-LO as a point of therapeutic intervention in Alzheimer's disease at the cerebrovascular level could possibly disrupt senile plaque formation in the underlying brain tissue before it starts.
As 5-LO is a membrane translocated enzyme and Vitamin E is known to reduce membrane fluidity, it should also be noted that the mechanism of inhibition could be physical rather than chemical. The decrease in membrane fluidity caused by the Vit E may not allow effective 5-LO translocation.
References:
Devaraj S, Jialal I. Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):1125-33. PubMed.
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