Alzheimer’s Disease (AD) and Oxidative Stress Relationship

Alzheimers Disease (AD) and Oxidative Stress RelationshipAlzheimers unsoundness (AD) is a neurodegenerative disease which bring forths a lethal twist in the geomorphologic wholeness, and a roadblock in the consort of mentality, this eventually channel the internet site to degeneration and shrinkage of brain, and override the control of brain over former(a) parts of the body, and pursues to the final closing remark of the disease- dying. Studies done on the paper have corroborated that the disease is non reversible, and the only patch of hope is diminish down its progress. But as the disease advances through mid item and evolves into severe AD, the condition of affected role becomes pathetic and care giving becomes to a greater extent painful. Studies have reported that notable symptoms of AD are seen only later on 60 years of age, even though the disease has started before that. sign symptoms are loss of short term memory- being forgetful close the recent events, and gradually over a time period of time patient seems to a greater extent absent minded about the environment, things which are chemically incised in the long term memory begins to be erased, and the final percentage point starts pushing the patient into severe AD which is tremendously pathetic.Studies have turn up that loss of function of neurons is the cause of AD. A closer look into the grimace revealed a obscure set of events that precede the neuronal degeneration- aerophilic underscore 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 scheme developed, and helped to hand much deeper into the inner workings and appliance of the disease. Hypotheses developed to explain mechanism of AD are amyloid cascade hypothesis, cholinergic hypothesis and tau hypothesis. mealy cascade hypothesis says, APP- Amyloid Precursor Protein, a transmemb rane 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 peptides which accumulates to form plaques- amyloid plaques- and bind to synapses closure the communication channel, eventually causes memory loss. According to cholinergic hypothesis, downward err in the levels of acetylcholine in brain is the cause for Alzheimers disease. Loss of function of cholinergic neurons was found in Alzheimers disease patients. Shift in the level of acetylcholine happens due to the lack of two enzymes involved in discount and breach down of acetylcholine. This will lead to loss of function of neurons brains functionality falls apart, and eventually leads to symptoms of Alzheimers disease. Tau hypothesis approaches the problem in another perspective, tau protein- a protein associated with microtubules in nerve cells- gets hyperphosphorylated, this enables cross conjoining among tau protein units, and they back withdraw from being attached to the microtubules. This causes loss of structural integrity of nerve cells, and they soften and clump to form drag ons- neurofibrillary tangles. Studies conducted focusing on the inner workings of these hypothesis 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 emotionale by non peptide bonds. In another study, amyloid peptides have shown close relation with some causes of mad cow disease. Studies cerebrate 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 let oning down of APP. APOE has variants, APOE4 is the one which codes for less active protein whose capacity to break down APP is sluggish. People with this variant gene are more run away 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 trauma leads to oxidization 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. oxidise derivatives impede with the channel of outline 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 effect from loosen r adical damage- but rapid heaping up of neurotoxic substances goes beyond control leading to severe imbalances, blockage of communication channels, and eventually death of neuron. Since mitochondria is the main source of palliate 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- buttocks 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. hue the nearby nerve cells, and the cycle goes on and gradually covers the brain and makes it office out of its normal being.