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Medical Forum / General / General / October 2005Novel hypothesis vicious circle involving iron / Alzheimer disease
Curr Neurovasc Res. 2005 Jul;2(3):261-7. Related Articles, Links Ferric cycle activity and Alzheimer disease. Dwyer BE, Takeda A, Zhu X, Perry G, Smith MA. Research Service, VA Medical and Regional Office Center, White River Junction, Vermont 05009, USA. barney.e.dwyer@dartmouth.edu Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage. PMID: 16181119 [PubMed - in process] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking Good post, two important points, a broken iron regulation system is proposed and too little iron in some tissues a related disorder. Just another nail, a counter example, in the coffin of the iron causes all disease because people eat meat idea. If iron causes the regulaton system to break then all people eating meat would get the disorder and too little iron is a direct body blow to the idea. In science when an idea fails we turn from it to find the truth elsewhere. "In science when an idea fails we turn from it to find the truth elsewhere." Exactly. Now try and convince the "essential fatty acid" true believers of this. I think you might win a fabulous cash prize if you do. Somebody posted the study of Asians who have high iron levels but not the "chronic disease" Western scientists expected them to have a few months ago, and I've posted Spiteller's explanation several times here, which is: "... lipid peroxidation (LPO) processes involve all PUFAs, not only arachidonic acid.Slight physiological changes of the cell wall for instance by proliferation seem to activate enzymes, e.g., phospholipases and lipoxygenases (LOX). When an outside impact (for instance by attack of microorganisms) exceeds a certain level LOX commit suicide and liberate iron ions. These start a nonenzymatic LPO. Enzymatic and nonenzymatic LPO distinguish fundamentally which has not been recognized in the past. In the enzymatic LPO processes peroxyl radicals generated as intermediates cannot leave the enzyme complex. In contrast in a nonenzymatic LPO process peroxyl radicals are not trapped. They attack nearly any kind of biological molecules, for instance proteins. Thus only the amount of an outside impact decides if proliferation, apoptosis, or necrosis is started.Some evidence indicates that cancer might be the consequence of a low response of cells to induce apoptotic LPO processes. In contrast to high level of LPO processes induces diseases combined with inflammation, for instance rheumatic arthritis. After consumption of food rich in linoleic acid its LPO products become increased in low density lipoprotein (LDL). This LDL is able to enter endothelial cells and damage cells from inside, long before an inflammatory response is detectable." Source: Med Hypotheses. 2003 Jan;60(1):69-83. "Are lipid peroxidation processes induced by changes in the cell wall structure and how are these processes connected with diseases?" Spiteller G. Lehrstuhl Organische Chemie, Universitatsstrasse 30, Bayreuth, Germany. gerhard.spiteller@uni-bayreuth.de > "In science when an idea fails we turn from it to find the truth > elsewhere." Blah, blah, blah, blah, blah! |
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