Posted at 11.28.2018
Alzheimer's disease (Advertising) is a neurodegenerative disease which in turn causes a lethal twist in the structural integrity, and a roadblock in the function of brain, this eventually route the problem to degeneration and shrinkage of brain, and override the control of brain over other parts of the body, and involves the final final remark of the disease- loss of life. Studies done on the topic have corroborated that the disease is not reversible, and the only patch of hope is slowing its progress. But as the condition advances through mid level and evolves into severe Advertisement, the condition of patient becomes pathetic and worry providing becomes more unpleasant. Studies have reported that well known symptoms of AD have emerged only after 60 years, even though the disease has started out before that. Primary symptoms are loss of short term ram- being forgetful about the recent situations, and gradually on the time period patient seems more absent -minded about the environment, things that happen to be chemically etched in the permanent memory commences to be erased, and the final stage starts forcing the individual into severe Advertising which is greatly pathetic.
Studies have turned out that lack of function of neurons is the reason for Advertising. A closer check out the aspect discovered a complex set of occasions that precede the neuronal degeneration- oxidative stress and imbalance in homeostasis, formation of roadblocks in communication, dropping apart of integrity and death of neurons. This enabled to exceed the results of superficial studies done and hypothesis developed, and helped to delve more deeply into the internal workings and system 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 Necessary protein, a transmembrane health proteins involved in main functions of growth, success and repair of nerve skin cells- is snipped at incorrect places by an enzyme called secretase, resulting in the formation of amyloid О peptides which accumulates to create plaques- amyloid plaques- and bind to synapses preventing the communication channel, eventually causes memory space loss. Relating 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 because of the lack of two enzymes involved in synthesis and breaking down of acetylcholine. This will likely lead to lack of function of neurons; brain's efficiency falls apart, and eventually leads to symptoms of Alzheimer's disease. Tau hypothesis approaches the condition in another perspective, tau protein- a necessary protein associated with microtubules in nerve cells- gets hyperphosphorylated, this allows cross linking among tau protein units, and they cool off from being mounted on the microtubules. This triggers loss of structural integrity of nerve skin cells, and they collapse and clump to create tangles- neurofibrillary tangles. Studies conducted focusing on the internal workings of the hypothesis have discovered that oxidative stress 's the reason that enhances plaque and tangle creation, repair mechanisms in cells cannot solve the situation as the oligomer creation and mix linking are predominantly created by non peptide bonds. In another review, amyloid О peptides have shown close relation with some factors behind mad cow disease. Studies related to genetics of Advertisement have found the hyperlink between APOE gene on chromosome 21 and the disease. APOE gene codes for apolipoprotein, and one of its functions is wearing down of APP. APOE has variants, APOEО4 is the one which codes for less lively necessary protein whose capacity to breakdown APP is sluggish. People with this variant gene are usually more tend to develop Advertising in later periods of life, and any abnormality related to chromosome 21 also results AD over a period.
To know more about the mechanism of disease and its own connection to oxidative stress, further studies did from different sides, and all the studies have come to a common point, the conclusions from all the studies stitched along gave a complicated and sophisticated picture about the system of the disease. Free radical destruction contributes to oxidation of products in cell. Oxidation causes new end products of glycation, nitration, lipid peroxidation, and oxidation of nucleic acids. These new end products chemically enhance other proteins and compartments inside the cell. Oxidized derivatives impede with the route of track elements, and imbalances their homeostasis, and allows protein like tau to form non peptide cross linking. In response to changes cell in the degrees of heme oxygenase-1 (HO-1)- an antioxidant enzyme to mitigate the bad results from free radical destruction- but fast heaping up of neurotoxic substances will go beyond control resulting in severe imbalances, blockage of communication stations, and eventually fatality of neuron. Since mitochondria is the primary way to obtain free radicals and oxidative precursors. Certain deletions in mtDNA led to change in normal levels and rates of metabolism and production of free radicals. Free radicals developed in mitochondria are temporary and they don't have the capability to cross membrane and reach cytoplasm to cause destruction, this led studies in a fresh course and found free radicals- OH- from cytoplasm- can strike guanidine in RNAs in cytoplasm which both can mix the membrane and reach into mitochondria, and cause imbalance and production of more steady H2O2- radicals which will come to cytoplasm and react with the route of trace elements, and starts off the primary occurrences for the significant reasons for Advertising to come into being. AD begins at neocortex portion of brain, and since the neurons pass away and rupture, the neurotoxic substances- plaques, free radicals, tangles, etc. - pervade the near by nerve skin cells, and the pattern continues on and gradually covers the mind and makes it slip out of its normal being.