The Development And Progression Of Amyloid

Alzheimer 's disease (AD) was discovered by a German doctor Alois Alzheimer in 1906 when he found amyloid plaques and neurofibrillary tangles in the autopsy of a woman who died of an unknown mental disease. The extracellular amyloid plaque deposits, composed of insoluble amyloid-Beta peptide were hypothesized to be the main etiological factor. “The most important abnormality is an excess of Amyloid-beta peptides brought about through either overproduction or failure in degradation.” (Uzun, Kozumplik, & Folnegović-Smalc, 2011) Later, it was discovered that intracellular neurofibrillary tangles composed of hyper-phosphorylated, helically-paired tau

Alzheimer 's disease (AD) is a progressive degenerative disease of the brain from which there is no recovery. There are three brain abnormalities that are the hallmarks of the Alzheimer’s disease is initially caused by plaques buildup in the brain’s neurons as illustrated in figure 1. The support structure that allows the flow of the nutrients through the neurons gets damaged and ultimately there is loss of connection among the neurons and they die off (National Institute of Health, 2015). This causes the brain tissue to shrinks, which is called atrophies. All this ultimately lead the victim of this disease to face difficulties in governing emotions, recognize errors and patterns, coordinate movement, and remember. Ultimately, a person with AD loses all memory and mental functioning.

Alzheimer’s disease is a prominent brain disease that effects a massive amount of individuals in the United States. Alzheimer’s disease (AD) is the sixth leading cause of death in the United States, accounting for 60-80% of dementia cases, with no chance of being cured, prevented or decelerating over time (Alzheimer’s Association, 2014). AD is the most well-known form of dementia, causing complications in brain function in the areas of memory, thinking, and behavior (Alzheimer’s Association, 2014). In an effort to gain a deeper understanding of Alzheimer’s disease, researchers create new knowledge about the disease, which is then distributed to the public. The goal in this information disbursement is to find new and inventive ways to treat AD, prevent AD from progressing at such a rapid pace, and aid in the quality of life in those diagnosed with AD as well as caregivers and medical professionals providing treatment to individuals’ with AD.

The chaperones have the main role of ensuring proper folding. When a chaperone protein becomes toxic, major changes in the conformation occur as the alpha helix becomes beta pleated sheets. The sheets now expose the hydrophobic amino acid and aggregation, or clumping together of sheets occurs (Borges, 2014).

Even today, after so much study, Alzheimer’s is not fully understood. However, researchers do agree that this degenerative disease is caused by the gradual buildup of fibrous protein compounds in the brain, which are known in the scientific world as amyloids. These amyloids in the brain area act like plaque and as a result of their presence, the normal brain functioning is disrupted.

Alzheimer’s disease is named after Dr. Alois Alzheimer who first discovered deviations from normal tissues of healthy individuals in the brain tissue of a lady in 1906. The woman, who showed symptoms of erratic behavior, loss of memory, and problems with communication, died of a then unfamiliar mental disorder. This led Dr. Alzheimer to investigate the cause of her unusual death. He assessed the brain of the woman and found that there were many anomalous masses (amyloid plaques) and intertwined bundles of fiber (neurofibrillary tangles). Scientists today have pinpointed the qualities of Alzheimer’s to be a) tangles in the brain (neurofibrillary tangles), b) plaque in the brain (amyloid plaques), and c) loss of connections among nerve cells.

The causes of Alzheimer’s are not yet fully understood; however, its effect on the brain can be understood. Alzheimer’s disease - insidious, attacking and terrifying - stalks and then murders brain cells. A brain afflicted with Alzheimer’s disease has a decreased count in cells and connections among cells. The more brain cells die, the smaller the brain of a person with Alzheimer’s gets. When doctors examine a brain with Alzheimer’s tissue, they see two types of deformities that are known to be trademarks of the disease. The first trademark is known as plaque, which is a cluster of a beta-amyloid protein that may damage and kill brain cells in a number of ways, including blocking with cell-to-cell communication. Whereas the final cause of brain-cell death in Alzheimer’s remains a mystery, the groups of beta-amyloids that cover the brain cells are a sure sign of the disease. The second trademark of Alzheimer’s is the tangle. Brain cells are reliant on internal support and a transport system to bring nutrients and other essentials to their distant regions. This system needs a protein called tau. In Alzheimer’s, strings of tau protein roll into abnormal tangles inside brain cells, concluding in failure of the cell's transport system. This breakdown of the system is powerfully involved in the decline and death of brain

There may also be sections where the secondary structure is neither helix nor sheet. Then the structure is called a random structure, indicating that it folds in random directions. The amino acids in an alpha helix are arranged in a right-handed helical structure resembling a spring. The alpha helix is the most common form of regular secondary structure in proteins. The beta-sheet is the second form of regular secondary structure in proteins consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. The beta-sheet is sometimes called the beta pleated sheet since sequential neighboring atoms are alternately above and below the plane of the sheet giving a pleated appearance. Turns are the third of the three "classical" secondary structures that serve to reverse the direction of the polypeptide chain. They are located primarily on the protein surface and accordingly contain polar and charged residues. However, they are not very common in discussions of protein structure today.

Amyloid Beta is a peptide of amino acids. This peptide has been found to be accumulating in the brains of those with Alzheimer's disease (AD), leading to one of the leading hypotheses as to what causes AD, the Amyloid Beta hypothesis. This hypothesis states that Amyloid Beta accumulation leads to a cascade event, which in turn begins to kills cells over time. This killing of cells leads to memory loss, and later death. Although this hypothesis is the most prominent, and believed to be the best amongst many experts, it does have its drawbacks. According to neurologists John Hardy and Dennis J. Selkoe one of the biggest concerns with this hypothesis is that “The most frequently voiced objection is that the number of amyloid deposits in the

Introduction: The goal of this experiment was to practice using the FirstGlance in Jmol molecular visualization to examine key structural features of proteins. This work is important because protein structure can be related to function, multiple-sequence alignments and evolutionary preservation, and designing drug. FirstGlance in Jmol makes it fairly easy to perceive structure-function relationships in the protein you chose. Using FirstGlance, it is easy to visualize and distinguish chains, and disulfide bonds are obvious. Alpha helices and beta strands are evident due to the "cartoon" secondary structural schematic.

Proteins play a critical role in normal human function and are made up of a sequence of amino acids that have to be precise, to allow for proper folding to a functional three dimensional structure (confirmation). This sequence is coded in the DNA in genes and hence any changes through mutation or allele combinations can cause a change in the protein(s) coded, resulting in a diseased state. Such a case is a disease called Cerebroarterial Amyloidosis, Icelandic type (CAI) that arises from a mutation on chromosome 20 in the CST3 gene located in the short arm of the chromosome (20p11.21).1 It is an autosomal dominant hereditary disease and the mutated gene leads to the protein translated (cystatin C) having a leucine being substituted with a Glutamine

The amyloid cascade hypothesis is the most widely accepted of the AD pathogenesis hypotheses. Its principle is that the accumulation of Aβ plays a major role in AD pathogenesis, and the disease is analyzed as a series of abnormalities in the process and secretion of the amyloid precursor protein (APP), where an inequality between production and clearance of amyloid β is the triggering event and the most important factor responsible for other abnormalities observed in AD (Hardy et al, 2002; Cummings et al, 2007). Amyloid β is a peptide with high resistance to proteolytic degradation. It consists of 37–43 amino acids with different isoforms (Deane et al, 2009). Aβ is the result of sequential cleavage of the amyloid precursor protein (APP), generating

Controlling the formation of beta-amyloid plaques by isolating somatic cells from a patient and creating a stem cell lineage by reverting the isolated cells back to stem cells using the iPS technique. This will allow the cells then to differentiate into neurons and other brain cells. This would allow for connections between neurons to re-develop when injected into a patient’s brain. One advantages to using this technique is the production of autologous cells that were reprogrammed from the patient’s own cells. This reduces the chance of rejection that is present in other stem cell infusions. To collect the somatic cells a mini liposuction procedure will be preformed near the lower abdomen. The extracted material will

Bettelheim, Brown, Campbell and Farrell assert that polypeptide chains do not extend in straight lines but rather they fold in various ways and give rise to a large number of three-dimensional structures (594). This folding or conformation of amino acids in the localized regions of the polypeptide chains defines the secondary structure of proteins. The main force responsible for the secondary structure is the non-covalent

Molecular chaperones stabilize unfolded or misfolded proteins until native conformations have been obtained to promote cell survival during and after stress conditions. They do not change or add to the folding principles encoded by a protein because polypeptide chains inherently carry within them all the information that is necessary for achieving the native state of a protein. Instead, they optimize the folding process by stabilizing folding intermediates and are involved in every aspect of proteome maintenance including de novo folding, refolding of stress-induced misfolded proteins, and targeting proteins for degradation (Hartl 2009, Hartl 2011). Chaperones, many of which are induced or upregulated only during stress conditions, work in cooperative networks when protein-aggregate concentration