Alzheimer’s Disease (AD) and Oxidative Stress Relationship

Alzheimer’s Disease (AD) and Oxidative Stress Relationship Alzheimer’s disease (AD) is a neurodegenerative disease which causes a lethal twist in the structural integrity, and a roadblock in the function of brain, this eventually channel the situation to degeneration and shrinkage of brain, and override the control of brain over other parts of the body, and comes to the final closing remark of the disease- death. Studies done on the topic have corroborated that the disease is not reversible, and the only patch of hope is slowing down its progress. But as the disease advances through mid stage and evolves into severe AD, the condition of patient becomes pathetic and care giving becomes more painful. Studies have reported that notable symptoms of AD are seen only after 60 years of age, even though the disease has started before that. Initial symptoms are loss of short term memory- being forgetful about the recent events, and gradually over a period of time patient seems more absent –minded about the environment, things which are chemically etched in the long term memory begins to be erased, and the final stage starts pushing the patient into severe AD which is tremendously pathetic. Studies have proved that loss of function of neurons is the cause of AD. A closer look into the aspect revealed a complex set of events that precede the neuronal degeneration- oxidative stress and imbalance in homeostasis, formation of roadblocks in communication, falling apart of integrity and death of neurons. This enabled to go beyond the findings of superficial studies done and hypothesis developed, and helped to delve much deeper into the inner workings and mechanism of the disease. Hypotheses developed to explain mechanism of AD are: amyloid cascade hypothesis, cholinergic hypothesis and tau hypothesis. Amyloid cascade hypothesis says, APP- Amyloid Precursor Protein, a transmembrane protein involved in main roles of growth, survival and repair of nerve cells- is snipped at wrong places by an enzyme called secretase, leading to the formation of amyloid ÃŽ ² peptides which accumulates to form plaques- amyloid plaques- and bind to synapses blocking the communication channel, event ually causes memory loss. According to cholinergic hypothesis, downward drift in the levels of acetylcholine in brain is the cause for Alzheimer’s disease. Loss of function of cholinergic neurons was found in Alzheimer’s disease patients. Shift in the level of acetylcholine happens due to the lack of two enzymes involved in synthesis and breaking down of acetylcholine. This will lead to loss of function of neurons; brain’s functionality falls apart, and eventually leads to symptoms of Alzheimer’s disease. Tau hypothesis approaches the problem in another perspective, tau protein- a protein associated with microtubules in nerve cells- gets hyperphosphorylated, this enables cross linking among tau protein units, and they back off from being attached to the microtubules. This causes loss of structural integrity of nerve cells, and they collapse and clump to form tangles- neurofibrillary tangles. Studies conducted focusing on the inner workings of these hypoth esis have found that oxidative stress is the reason that enhances plaque and tangle formation, repair mechanisms in cells are unable to solve the situation as the oligomer formation and cross linking are predominantly made by non peptide bonds. In another study, amyloid ÃŽ ² peptides have shown close relation with some causes of mad cow disease. Studies related to genetics of AD have found the link between APOE gene on chromosome 21 and the disease. APOE gene codes for apolipoprotein, and one among its functions is breaking down of APP. APOE has variants, APOEÃŽ µ4 is the one which codes for less active protein whose capacity to break down APP is sluggish. People with this variant gene are more tend to develop AD in later stages of life, and any abnormality related to chromosome 21 also results in AD over a period of time. To know more about the mechanism of disease and its attachment to oxidative stress, further studies have done from different angles, and all the studies have come to a common point, the findings from all the studies stitched together gave a complex and elaborate picture about the mechanism of the disease. Free radical damage leads to oxidation of products in cell. Oxidation leads to new end products of glycation, nitration, lipid peroxidation, and oxidation of nucleic acids. These new end products chemically modify other proteins and compartments inside the cell. Oxidized derivatives impede with the channel of trace elements, and imbalances their homeostasis, and enables proteins like tau to form non peptide cross linking. In response to changes cell up the levels of heme oxygenase-1 (HO-1)- an antioxidant enzyme to mitigate the bad effects from free radical damage- but rapid heaping up of neurotoxic substances goes beyond control leading to severe imbalances, blockage of communicati on channels, and eventually death of neuron. Since mitochondria is the main source of free radicals and oxidative precursors. Certain deletions in mtDNA resulted in change in normal levels and rates of metabolism and production of free radicals. Free radicals formed in mitochondria are short lived and they do not have the ability to cross membrane and reach cytoplasm to cause damage, this led studies in a new direction and found free radicals- OH from cytoplasm- can attack guanidine in RNAs in cytoplasm and this both can cross the membrane and reach into mitochondria, and cause imbalance and production of more stable H2O2 radicals which can come to cytoplasm and react with the channel of trace elements, and starts the primary events for the major causes for AD to come into being. AD starts at neocortex area of brain, and as the neurons die and rupture, the neurotoxic substances- plaques, free radicals, tangles, etc. pervade the nearby nerve cells, and the cycle goes on and graduall y covers the brain and makes it slip out of its normal being.

A Clausewitzian Analysis of the Thirty Year’s War Essay

When applying the Clausewitzian paradoxical trinity paradigm to the Thirty Year’s War, we see that the catalyst that sparked much of the conflict during that time was driven by civil unrest of the ‘People’ engendered by fear of religious persecution. Beginning with the divergence of religious and secular leadership resulting from the Protestant Reformation which was exacerbated by the rigidity of Catholic monarchy, we see how widespread fomenting dissent within the German States lead to the decline of the Habsburg ruling family. In his work, On War, Clausewitz describes the essence of war as a continual interplay between the ‘paradoxical trinity’ of the people, the government, and the military. As we apply this framework to the complex and varied influences of the early 17th century, this model provides clarity in determining the root causes that shaped this era – an era that has come to be characterized by the rampant internecine warfare of religious and political factions of the time. The Protestant Reformation, which had begun to take traction with many of the expansion-minded German nobility, set the stage for the conflict between Catholic and Protestant factions throughout the German Provinces. With the signing of the Peace of Augsburg in 1555, Lutheranism had been officially recognized by the Holy Roman Empire. The major outcome of this treaty enabled the Protestant movement in Germany to claim lands once belonging to the Catholics. This result had great appeal to the more secular rulers throughout Europe who sought to disentangle themselves from papal oversight and influence. Under the rule of the Holy Roman Emperor Mathias, Protest and Catholic factions had gained equity of representation and influence throughout the Hapsburg controlled regions. This unification was driven, in part, by the larger Muslim threat presented by the Ottoman Empire. This truce, however, was an uneasy one with all the characteristics of a 17th century Cold War between the two religious sects, and as the balance shifted with the rise of a new monarch, each side began an arms race to defend their interests from the other. The appointment of the intransigent Catholic monarch, Ferdinand II, posed a threat to Protestants throughout the various Habsburg controlled territories. Religious hegemony of individual States was the preferred condition of German rulers in the early 17th century. The religion of the ruler shall be the religion of his subjects† was a motto that was very near and dear to many of the European rulers of the day. This rang especially true among the Catholic territories where the Church exercised much greater political influence than their Protestant counterparts. So when the balance of Protestant and Catholic controlled States was disrupted with the ascension of Ferdinand II – a widely acknowledged Catholic zealot – to the throne of Bohemia it brought a face to the fears of the Protestant nobility. In an effort to limit his religious edicts, the Protestant Bohemians entreated for religious freedoms of their newly throned monarch. The harsh dismissal of these entreaties was the spark that ignited the powder keg that Central Europe had become, and the subsequent â€Å"Defenestration of Prague† resulting in the death of Ferdinand’s representatives by Protestant rebels signaled the start of uprisings in Hungary, Transylvania, and the rest of Bohemia. This uprising spread throughout Europe, drawing in both political and religious powers to become decisively engaged. The unresolved religious dissent among the people and the Habsburg ruler served as a lodestone for conflict throughout Europe and lead ultimately to the decline of the Holy Roman Empire into several small autonomous territories. Early successes by the Hapsburg against the Bohemians, and later the Palatinate States, led to the direct involvement of France and Holland allying against the Hapsburgs. Their efforts were later supported by England, Sweden, Denmark, Savoy and Venice. These State actors all had their own agendas but ostensibly acted in support of the Protestant rebellion whose secular distancing from Church control appealed to both the ruling classes and commoners alike. The war ravaged the German countryside and some estimates have nearly half of the population were killed, wounded, or displaced, with some areas such as Wurttemberg losing nearly 75% of their population. The Peace of Westphalia which was signed in the fall of 1648 signified the end of the war. Alsace became part of France, while Sweden gained much of the German Baltic coast, while the Emperor had to recognize the sovereign rights of the German princes, and equality between Protestant and Catholic states, while Spain, in a separate peace, finally acknowledged the independence of the Dutch Republic. † The Habsburg crown was now, more than ever, subject to the auspices of the Imperial Diet, also termed the Reichstag or German Parliament, which exists to this day. When viewing the root cause of the Thirty Year’s War under the Clausewitzian perspective, we see that the â€Å"People† node of the paradoxical trinity was the most influential during that time. This war is often termed the War of Religion as religion was either the root cause of conflict, or the excuse used to mask political machination in efforts to expand power and influence. But in truth, religion was merely the vehicle by which contention among the commoners and landowners took shape to facilitate change of the current governmental structure. Upon the conclusion of the war, after the smoke had cleared and the damage was tallied, Habsburg power was irrevocably shattered and France emerged as the new epicenter of European influence and might. But the consequences extended beyond the immediate outcomes of the war. The resulting Peace of Westphalia changed the very relationships between citizens and the State, extricating religion from the government and laying the foundation for modern civic relationships of today’s democracies.

Macbeth Instruments of Perversion Essay - 1239 Words

Surreal, unexplainable, bizarre, dreamlike. Terms such as these are often used to describe the feelings associated with Shakespeares Macbeth. These unreal qualities are the result of numerous twisted perversions in the plot and characters. Macbeth and Lady Macbeth are chased by equivocation, trying to balance out reality and their dream-world though they are entrenched in a fog of uncertainty and doubt. Macbeth himself quickly becomes an instrument of this distortion due to the influences of the Weird Sisters, Lady Macbeth, and the unstoppable chain of events his initial violence sets off. Macbeth is constantly in a state of dreaming, thought he does not realize it. In fact, most of the time, he cannot tell the difference between†¦show more content†¦Macbeth does murder sleep (2.2.47-48). Secondly, there is blood mentioned or spilled throughout the play; something that should be kept inside the body is repeatedly found outside. The play opens with Scotland at the end of a war and Macbeth as her savior. A soldier reports that Macbeth had personally unseamed [an enemy soldier] from the nave to th chops/ And fixed his head upon our battlements, displaying Macbeths ability to take part in violent acts (1.1.24-25). Macbeths ambition is the cause of this willingness to kill, and his ambition is materialized in the form of the crown of Scotland. The crown is the third found confusion because of the question of where the power behind the crown is from. Whether power comes from divine right, outside the body, or through the blood of the previous king, inside the body, is challenged in Macbeth, by Macbeth himself and his ambitions of taking control and by the Weird Sisters in naming Banquos sons the future Kings of Scotland (1.3.51-53). It is because of the prophecies of the Weird Sisters that Macbeth even starts thinking of taking control of the crown, though some still maintain he would have stumbled upon the notion of murder had they not put the idea into his head. Upon naming Malcolm the Prince of Cumberland, Macbeth decides to take matters into his own hands and begins the downward spiral of confusion (1.4.55-60). It should be noted that before meeting the Weird Sisters, MacbethShow MoreRelated William Shakespeares Macbeth Essay1887 Words   |  8 PagesThe Witches or Weird Sisters play a major role in the brilliant trage dy Macbeth by William Shakespeare. The role of the Weird Sisters represents that equivocal evil in the nature of things which helps to deceive the human will. They are not mere witches although they have some of the powers of witches. Even though they were produced by nature, they share with angels a freedom from limitation of space and time, a power to perceive the causes of things, and to see some distance into human minds (KermodeRead MoreMacbeth Dreams Visions and Hallucinations Rereading2477 Words   |  10 PagesThe influence of Dreams, Visions and Hallucinations in Macbeth and other Literary Texts â€Å"The realities of the world affected me as visions, and as visions only, while the wild ideas of the land of dreams became, in turn,—not the material of my every-day existence--but in very deed that existence utterly and solely in itself.† ---- Edgar Allan Poe Uncanny encounters with visions and hallucinations blur the presumed constraints of time and space. The ‘phantasms’ or sensory impressionsRead MoreEssay on Macbeth and the Gunpowder Plot of 16054662 Words   |  19 PagesMacbeth and the Gunpowder Plot of 1605 Shakespeare’s Macbeth was influenced by the gunpowder plot of 1605. The equivocation that was inspired by this event played an important role in the play. The general theme of Macbeth reflects the mood of society at the time that it was written. This relationship is a direct reflection of the mimetic theory. This paper will examine the Gunpowder Plot of 1605 and the role of equivocation in the subsequent prosecutions during the time that Shakespeare was

Significance Of Marco Polo s Voyages - 1136 Words

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