Protein misfolding and aggregation is associated with an increasing number of highly debilitating human diseases, including Alzheimer's disease, diabetes and some types of cancer [1]. The proteins involved in these disorders are different and not related in evolutive, sequential or structural terms [2]. However, in all the cases, misfolded conformers of these polypeptides establish non-native intermolecular contacts that result in their deposition into insoluble amyloid aggregates in the intra or extracellular space [3]. Amyloid fibrils are highly ordered and repetitive structures where all polypeptides adopt a common fold [4,5]. They are thread-like protein aggregates with a core region formed by repetitive arrays of β-sheets oriented perpendicularly to the fibril axis forming a structure known as cross-β because it displays two sets of characteristic X-ray diffraction signals, forming a “cross” pattern [6]. These particular fibrils have diameters of ∼10 nm and often consist of multiple proto-filaments twisted around the fibril axis. Importantly, the ability to form amyloid-like structures is not restricted to a subset of disease-linked proteins and this conformation may be accessed by most, if not all, human proteins, irrespective of their native fold [7]. In fact, the molecular interactions leading to the formation of amyloids are similar to those promoting the folding and functional assembly of proteins. As a result, folding and aggregation pathways are continuously competing in the cell [8,9]. This implies that the protein partners involved in conformational disorders might me much larger than previously thought [10], neuronal receptors among them. Prediction of protein aggregation Although any polypeptide has the potenti... ... middle of paper ... ...) is based on the physico-chemical principles of β-sheet formation extended by the assumption that the core regions of an aggregate are fully buried[24]. 3) Aggrescan (http://bioinf.uab.es/aggrescan/) is based on an aggregation propensity scale for natural amino acids derived from in vivo experiments and on the assumption that short and specific sequence stretches modulate protein aggregation [25,26]. 4) Amylpred (http://biophysics.biol.uoa.gr/AMYLPRED/) is a consensus predictor of amyloid propensity that integrates the results of five different methods in a single output to detect the regions in a protein with the highest intrinsic propensity to form amyloids[27]. As a stringent criterion for identification of aggregation-prone regions we have considered as positive hits only those regions recognized simultaneously by at least three of these algorithms.
structures called plaques. In Alzheimer's disease, similar plaques develop, but they are composed of fragments of a different protein.
Yu H. (1999). Extending the size limit of protein nuclear magnetic resonance. Proceedings of the National Academy of Sciences. 96 (2), pp. 332-334.
Creutzfeldt-Jakob is a fatal, progrossive and incurable neurologic disorder which affects the brain in a destructive way. Globally, it attacks one person in every one million people. Specifically, at United State there are more than 300 cases per year. However, it is extremely complicated to diagnose, so the number of cases might get higher in the future. CJD (Creutzfeldt-Jakob disease) symptoms usually occur in later life for women and men whose ages are between 60 and 70. This essay displays a definition of Creutzfeldt-Jakob disease based on its identity, causes, symptoms, risk factors and treatment.
To find the culprit to stop tau proteins and amyloid peptides to function improperly, scientists realized that studying brains at an earlier age when they are alive would be best in their search to find a cure. Studying living brain tissue would introduce a lot more discoveries that dead brain tissue would not offer. Techniques like magnetic resonance imaging (MRIs) and position emission tomography (PETs) are actually not as helpful in studying living brain tissue because they can provide up to a millimeter of focus on the brain but that would not be adequate to find the formation of the plaques and tangles which need more concentration to about a tenth of a milliliter. But there are new tools like the multi-photon confocal microscope that is better and more precise in looking at brain activity. Also the approval of Amyvid by the FDA has allowed for easier visuals on PET scans because its purpose is to dye the amyloid proteins that could not be seen in regular PET scans. From these astounding innovations, scientists are close to developing genetic tests that could determine the risk of an individual developing Alzheimer’s
Prion proteins are small infectious particles that are formed by the miss-folding of the protein structure. It is believed the miss-folding of such proteins has been the cause of disease such as Bovine spongiform encephalopathy in cows and Creutzfeldt-Jakob disease in humans. The prion proteins that are known to mankind so far suggest that they affect the brain of the affected individual. “A study1 in the British Medical Journal reveals that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes variant Creutzfeldt–Jakob disease (vCJD).”(Callaway, 2013). The study therefore shows that a high number of people are at risk and this is a cause for concern as the prion protein which is miss-folded prompts normal proteins present in the brain, to alter their structure so they also become miss folded. The miss folded structure is understood to be very stable and as levels of the protein build up within the infected tissue this results in destruction and eventually death of the cell. The prion protein, PrP is thought to be the cause of all mammalian prion diseases but the structure of the protein is yet to be discovered. The normal cellular form of the prion protein is PrPc, whereas the miss folded scrapie form is PrPSc. PrPc is constructed from 209 amino acids and one disulphide bond and are found on cell membranes. “Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms.”(Hedge et al, 1998). The miss folded form, PrPSc has more Beta sheets however the normal form PrPc has Alpha structure present. “Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were c...
Schulman, Joshua M., and David E. Fisher. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 28 Aug. 0005. Web. 24 Apr. 2014.
induce the formation of an amyloid fold, in which the protein polymerizes into an aggregate consisting
Clinically, Alzheimer’s disease is characterized by the accumulation of beta-amyloid plaque between living neurons in the brain (Sabbagh, 2008). This results in an excessive calcium influx inside the neurons and the breakdown of a protein called tau. Normally, the rol...
Alzheimer’s disease got its name from the German doctor, Dr. Alois Alzheimer. In 1906, he noticed that there were abnormal clumps and bundles of fibers i...
Scientists know that Alzheimer disease is characterized by a gradual spread of sticky plaques and clumps of tangled fibers that disrupt the organization of nerve cells in the brain. However , a definite cause, prevention, or cause has not been found.
"The Species of the Secondary Protein Structure. Virtual Chembook - Elmhurst College. Retrieved July 25, 2008, from http://www.cd http://www.elmhurst.edu/chm/vchembook/566secprotein.html Silk Road Foundation. n.d. - n.d. - n.d.
The Alzheimer’s Association (2005) defines the disease as “a progressive brain disorder that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate, and carry out daily activities”. Contrary to popular belief, Alzheimer’s is not the result of normal aging, although it normally occurs more frequently in people who are over the age of 65 (Gruetzner, 1988). Studies performed on the brains of deceased Alzheimer’s patients show several irregularities. The most obvious abnormality is in the signal-transmitting chemicals, where a 40-90% decrease in the enzyme CAT is found. This enzyme lies in the cerebral cortex and hippocampus regions of the brain. When CAT is decreased, it causes cholinergic or acetylcholine-releasing nerve terminals to diminish. These chemicals are important for communication between nerves. Also found during these autopsies were double strands of neurofibullary tangles, senile plaque (decayed neural material), and granulovacular degeneration-all which are associated with mental impairment. Neurofibullary tangles normally do increase with age, but Alzheimer’s patients show a very high density of the tangles. The brain has also been found to contain abnormally high concentrations of aluminum (Weiner, 1987).
Alzheimer’s disease or AD is an incurable disorder of the brain that results in loss of normal brain structure and function. In an AD brain, normal brain tissue is slowly replaced by structures called plaques and neurofibrillary tangles. The plaques represent a naturally occurring sticky protein called beta amyloid and in an Alzheimer’s brain, sufferer’s tend to accumulate too much of this protein. Neurofibrillary tangles represent collapsed tau proteins which, in a normal brain along with microtubules, form a skeleton that maintains the shape of the nerve cells. In Alzheimer’s disease, the tau proteins break loose from their normal location and form tangles. Without the support of these molecules, nerve cells collapse and die. As normal brain structure is lost with progression of the disease, brain function also degenerates. Patients afflicted with Alzheimer’s disease display a gradual mental decline. Initially, and most apparently, there is a loss of short-term memory. Eventually, as a patient progresses to later stages of the disease, the brain becomes so damaged that patients can no longer communicate or recognize immediate family or even themselves. They have difficulty walking and standing and frequently fall. In the final stages, they lose bladder and bowel control and have difficulty with swallowing, frequently leaving them malnourished and dehydrated. Eventually, they are forced to remain bedridden and, without the help of life-prolonging measures provided in a hospital, die. However, this level of deterioration is severe and may take as long as twenty years. Because of the disease’s slow progress and its usual later start in a person’s life, a victim of AD will usually die first of natural causes. Under the objectives ...
Mann, M., 2013. Mind Action Series Physical Sciences 12 Textbook and Workbook. Sanlamhof: Allcopy Publishers.
Alzheimer’s Disease is named after a German doctor, who specializes in the brain and nervous system, named Alois Alzheimer. This Disease forms in the brain. Alzheimer’s is the most common form of Dementia, a general term for memory loss and other intellectual abilities serious enough to enter. The Tau protein ensures the tubes in your brain stay straight allowing molecules to pass through freely. In Alzheimer’s Disease the protein collapses into strands or tangles, making the tubes disintegrate. There is visible differences of brain tissue in the from misfolded proteins called plaques and tangles. Beta-Amyloid clumps block signals and communication between cells in the brain. Researchers agree that Alzheimer’s Disease is m...