Nitration+Tau+Protein+in+Alzheimer's+Disease

= = This was a topic that i thought about but i couldn't really decide whether or not I should do this topic. I decided to keep some info here in case i ever do want to switch at the very last minute. Plus, it's useful for future references.

So, i decided not to do my original GA article last minute. Although I am fascinated with neurogenesis, neurodegeneration fusion of neuro-immuno systems. I decided to change my topic to something much more defined. My main motivation for changing it is because the pharmaceutical company that makes GA is not releasing its structure. It's just not helpful. I have a over 20+ resources on GA and the activation, the mechanisms, but i feel like it doesn't do me any good if i just mention the mechanism without an explanation of how it works. I loved the article by Aharoni et al., but when i looked in to more recent literature, it didn't provide enough information other than a predicted mechanism of action.
 * The Effect of Protein Tyrosine Nitration in the Tau Proteins as One of the Major Contributing Factors to the Pathogenesis of Alzheimer's Disease.**
 * November 3, 2009**

So I changed my topic to **The Effect of Protein Tyrosine Nitration in the Tau Proteins as one of the major contributing factors in the Pathogenesis of Alzheimer's Disease**. Im going to write about my article about a review that I read the other day: The Role of Protein Tyrosine Nitration in Neurodegenerative Diseases and Atherosclerosis (Lee, J. et al 2009).

Role of Protein tyrosine Nitration in Neurodegenerative Diseases and Atherosclerosis
Tyrosine is a ubiquitous amino acid found in many proteins; however, nitration of the R subunit of tyrosine is the biological mechanism that causes disease. Nitration is characterized by reactive nitrogen species (RNS), NO•, and reactive oxygen species (ROS). Nitration (-NO2) at the ortho position causes a more negative R subunit and a physiological pH shifts the structure of the protein causing malfunction, which leads to a decrease in protein activity. Tyrosine nitration is naturally seen in cells and may be involved in a variety of functions that include cell signaling or the mark of protein degradation. Understanding the tyrosine structure after subsequent nitration is heavily studied to determine it’s exact role in the pathology of many diseases. However there is little information regarding the mechanisms of endogenous RNS and ROS species. One RNS that is known to affect protein tyrosine nitration to form nitrotyrosine (3-NT) is the formation of ONOO-. Formation of this compound is caused by an increase in NO• and subsequent ROS interaction, O2-. Because of ischemia post reperfusion Production of NO• is produced via eNOS and iNOS through an independent pathway. Three independent pathways are described succeeding NO• formation and ROS reaction to produce ONOO-. This compound can either react in one of three ways: release a radical O and react with hydrogen peroxide to form an NO2•; combine with CO2 to produce carbonate and produce NO2•; react with H+ to make ONOOH with a subsequent release of •OH to form a NO2• Using mass spectrometry, WB, 2-D PAGE, and IP identified these nitrated proteins. Site specific loci – such as phosphorylation sites on kinases – were reported, however the nitration-catylizing enzyme was not reported and is a future direction in the series of experiments. What is known is with a change in the protein’s isoelectric point, changes the conformation and changes the functionality of the protein and of the 111 identified 3NT proteins, 34 were isolated and studied in vivo. Three major nitrated proteins, tau, alpha-syn and LDL have been extensively studied. During in vivo studies, aged animals exhibit an increased sensitivity to stochastic debris that lead to inflammatory stimuli. In Alzheimer’s Disease (AD), 3NTs as well as 3,3’-dityrosine levels are significantly increased leading to subsequent neurofibrilary tangles (NFTs) and increased inflammation. This suggests that ROS and RNS cause the nitration of tau, a subunit in the formation of NFTs. Both nitro-TYR 18 and 29 are found to show nitration, and exposing the hydrophobic chain to the hydrophilic environment, causing tangles. Decreased solubility of nitrated alpha-syn can be found in Lewy bodies, one of the hallmarks in Parkinson’s Disease (PD) pathogenesis. Nitration of the alpha-syn follows a similar pathway as the AD tau nitration with protein defunctionality. Studies of Tyrosine Nitration in Cardiovascular diseases were conducted using 2-D page and WB, and other assays similar to Nitration in Neurodegenerative Diseases. The general results, "are consistent with age-dependent increased oxidative stress and with free radical-dependent nitration of proteins, possibly suggesting that age-dependent protein nitration is responsible for age-dependent degeneration and functional decline of heart proteins." Due to inflammation, ROS and RNS, from vascular smooth muscle, react. Exact mechanisms are still being uncovered; for example CD40L's mechanism of inflammation. One mechanism that is known using CD40L as an intermediate to inactivate PGIS nitration, which inactivates symptoms of atherosclerosis and lead to vasodilation and anti coagulating abilities. LDL proteins have also been analyzed and nitrated LDLs increase inflammation and induces atherosclerosis. The nitration mechanism and signal transduction of nitrated LDL, resulting in atherosclerosis. Also inhibition of nitration is seen to also react with arterial walls and lead to coronary artery disease. Protein Tyrosine nitration is seen in biological examples and has a significant biological importance due to its role in age-related diseases. Isolation of Nitrated proteins are analyzed mostly by 2D-PAGE and the species have been performed in vitro and in vivo. Thus, because of nitration, proteins lose their structural functionality and become pathogenic in neurodegenerative diseases and cardiovascular diseases.
 * Introduction:**
 * Pathways of Protein Tyrosine Nitration :**
 * Proteomic Identification of Nitrated Proteins**
 * Protein Tyrosine Nitration on Neurodegenerative Diseases**
 * Protein Tyrosine Nitration in Cardiovascular Diseases**
 * Conclusions**

[|[DOI]]
 * [Full Marks JCB]**

**Possible Outline:**
-Overview of Neurons structure and function also introducing certain names that are associated with neurons. ie cell body is typically called the soma. -Overview of Neurodegeneration -History of Alzheimer's Disease -Physiological changes in AD patients -Psychological changes in AD patients -The Pathogenesis of AD - Proteolytic Cleavage of APP to form A-beta - Tau Proteins Neurofibrilary tangles -Nitration pathway -general pathway -eNOS, iNOS,and NOS -RNS and ROS why NO• is normal as an Neurotransmitter (NT) -How it plays a role in Neurofibrilary tangles (this will be really long)