José Ángel Pagán LópezNovember 13, 2009Biol 3095-142<br />-Amyloid Oxidative Stress and free radical theory in Alzheimer...
Oxidative stress……………………………………………………………3
Free radical theory……………………………………………………...….4</li></ul>d.   Amyloid……………………………………………………………….4<br />IV. Conc...
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Review Paper

  1. 1. José Ángel Pagán LópezNovember 13, 2009Biol 3095-142<br />-Amyloid Oxidative Stress and free radical theory in Alzheimer Disease Brain<br />Table of Contents<br />I. Abstract………………………………………………………………….…………..1<br />II. Introduction………………………………………………………………………1-2<br />III. Body<br /><ul><li>Alzheimer Disease………………………………………………………2-3
  2. 2. Oxidative stress……………………………………………………………3
  3. 3. Free radical theory……………………………………………………...….4</li></ul>d. Amyloid……………………………………………………………….4<br />IV. Conclusion………………………………………………………………………4-5<br />V. Cited References…………………………………………………………………...5<br />Abstract<br />The discovery of the AD had made an eminent challenge in finding a probable cure for this dementia. The mayor outcome of this disease is the myloid proteins. These proteins increase with the rate of age. Radical theory is present in this disease, specifically in  amyloid proteins, produced by oxidative stress. With a lot of factors contributing to AD like: aging, production, fibrillization, and others there’s no available cure to the disease.<br />Introduction<br />The case presented by the German physician Alois Alzheimer, of a woman with 51 years, that presented a severe remembrance, behavior, and language complications, marked the discovering of the disease. After that the woman died, the autopsy revealed a shrunken brain and abnormalities in brain cells. This disease is Degenerative and terminal and the most common dementia that affects 26 millions of worldwide (Alzheimer Association 2008). This dementia doesn’t have a cure and has different cognitive variations in the patients like: psychological symptoms, behavior, functioning, and the impact of the caregivers, making the possible solutions difficult to find. <br />A mayor factor contributing to the disease is the oxidative stress that is the empowerment of the antioxidant defense structure by the oxidative system. This stress is produced by free radicals. Chauhan states that: “Oxidative stress plays an important role in neuronal degeneration in AD. Soluble ,  fibrils, NFT, and mitochondrial abnormalities increase neurological disorders. The free radicals that produce this disorder are the (ROS) reactive oxygen atoms, showing enlarged levels of lipid peroxidation.” (Chauhan 2006). <br />Alzheimer Disease<br />As discussed, one of the mayor issues of the disease damages, consist in  proteins. The protein production increases with age, but along with AD, the proteins will have larger damage. Also senile plaques, neurofibrillary tangles are present in the area damage. In the cores of the plaques are located the Amyloid B proteins, which increases in the same rate as the (NFT). The main developers of the Alzheimer disease are the: Aging, fibrilization,  production, NFT pathology. The figure.1: preset the mechanism of AD. The part (A) present: the balance of the Reactive Oxygen Species (ROS) and the method of defense. In part (B): factor that induce AD are more present than the ROS defense. (Chauhan 2006).<br />Fig.1: Mechanism of AD (Chauhan 2006),<br />Oxidative Stress<br /> The brain is the most aerobical organ in the body. It uses 20% of the oxygen of the organism. In other hand the brain is rich in polyunsaturated fatty-acid, which enclose more chances to oxidize. The sources of the brain oxidation are the metals and mitochondrial factors. An overload in transition metals like zinc, copper and iron are seen in hippocampus, neocortex, and olfactory bulb in patients of AD (Moreira 2008). The mitochondrion plays a crucial role in the development of the oxidative stress. The fabrication of energy in ATP is also along with the formation of the ROS as product of the oxidative phosphorilation. Next to the ages the ROS increases making the chances of AD more critical. A review by (Alliev 2008) shows  deposition with mitochondrial abnormalities in the vascular walls of an overexpressing ABPP transgenic mouse. Furthermore, a gene expression profile was carried out in an ABPP transgenic mouse model in order to establish which genes may be critical for cellular changes in AD progression. In addition, (Aliev 2008) demonstrated a decrease in mitochondrial membrane potential and a reduction in ATP levels in neurons of an ABPP transgenic mouse model when compared to littermate non-transgenic mice.<br />Free Radical Theory<br />Most radicals that participate in the oxidative stress are the (ROS), they are: nitrogen and oxygen molecules with unpaired electron, these are unstable and reactive. They search and grab other electrons from biomolecules making the molecule a free radical to, creating a domino effect. Some of the molecules that are affected are the lipids, the nucleic acids, and proteins. They destruct the transport, the enzymatic activity, the fluidity and cross-linking. Excessively stress result in cell death. A review of (Moreira 2008) clarifies that morphometry of electron micrographs demonstrated mitochondrion abnormalities closely associated with AD. <br />Aß -Amyloid<br />The Beta Amyloid, is a peptide of 39-42 aminoacids. Two mayor sites have activity towards oxidation, histidine and tyrosine. In mentioned sites they chelae transition metals ions. The other active site is the methionine, it reduces metals to low valency forms. Studies by (Kontush 2001) observed that copper had efficient catalysis oxidation than other metals. These ions are extremely dynamic oxidants and they can catalyze further oxidation of biomolecules. For instance, they produce highly reactive hydroxyl radicals from hydrogen peroxide, an important by-product of mitochondrial electron transport. Phosphorilating the microtubulin-binding has a role in the function organization of the neuron, in axonal morphology, polarity and growth. <br />Conclusion<br />With the oxidative stress playing an important role in the progression of AD and with the mitochondrial damage, it can be found a way of delay the process of oxidation. There must be a path to synthetize a protein that has more affinity to transition metal ions, in a way that the  amyloids will have a balance of production with the ROS, preventing the progression of the AD. <br /> <br />Cited References<br />Aliev G, Smith MA, de la Torre JC, Perry G. 2004. Mitochondria as a Primary Target for Vascular Hypoperfusion and Oxidative Stress in Alzheimer’s Disease. Mitochondrion 4(2004):249-663. <br />Alzheimer Association. 2008. 2008 Alzheimer’s Disease facts and figures. Alzheimer’s & Dementia 4(2008):110-133.<br />Butterfield DA, Lauderback CM. 2002. Lipid Peroxidation and Protein Oxidation in Alzheimer’s Disease Brain: Potential Causes and Concequences Involving Amiloyd B-Peptide-Associated Free Radical Oxidative Stress. Free radical Biology & Medicine 32(11):1050-1060.<br />Butterfield DA, Perluigi M, Sultana R. 2006. Oxidative Stress in Alzheimer’s Disease Brain: New Insights from Redox Proteomics. European Journal of Pharmacology 545(2006):39-50.<br />Chauhan V, Chauhan A. 2006. Oxidative Stress in Alzheimer’s Disease. Pathophysiology 13(2006):195-208. <br />Kontush A. 2001. Amyloid-B: An Antioxidant that Becomes a Pro-Oxidant and Critically Contributes to Alzheimer’s disease. Free Radical Biology & Medicine 30(9):1120-1131.<br />Montine TJ, Neely DM, Quinn JF, Beal MF, Markesbery WR, Roberts LJ, Morrow JD. 2002. Lipid Peroxidation in Aging Brain and Alhzeimer Disease. Free Radical Biology & Medicine 33(5):620-626.<br />Moreira PI, Nunomura A, Nakamura M, Takeda A, Shenk JC, Aliev G, Smith MA, Perry G. 2008. Nucleic Acid Oxidation in Alzheimer Disease. Free Radical Biology & Medicine 44(2008):1493-1505.<br />Moreira PI, Santos MS, Oliveira CR, Shenk JC, Nunomura A, Smith MA, Zhu X, Perry G. 2008. CNS & Neurological Disorders – Drug Targets 2008(7):3-10.<br />Pratico D. 2002. Alzheimer’s Disease and Oxygen Radicals: New Insights. Biochemical Pharmacology 63(2002):563-567.<br />Vina J, Lloret A, Valles SL, Borras C, Badia MC, Pallardo FV, Sastre J, Alonso MD. 2007. Mitochondrial Oxidant Signalling in Alzheimer’s Disease. Journal of Alzheimer’s Disease 11(2007):175-181.<br />Zhu X, Raina AK, Lee H, Cassadesus G, Smith MA, Perry G. 2004. Oxidative Stress signalling in Alzheimer’s Disease. Brain Research 100(2004):32-39.<br />

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