Essay On Protein Misfolding

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 is one of the most common causes of dementia. The term 'dementia' describes a set of symptoms, which can include memory loss, changes in mood and problems with communication and reasoning. These symptoms occur when certain diseases and conditions, including Alzheimer’s disease, damage the brain. Alzheimer's disease could be described as a physical disease affecting the brain. During the course of the disease, protein 'plaques' and 'tangles' develop

A protein has multiple existing structures, these are the primary, secondary, tertiary and quaternary structures which occur progressively. A protein is essentially a sequence of amino acids which are bonded adjacently, and interact with one another in various ways depending on the R group that the amino acid contains. There are 20 different amino acids which are able to be arranged in any given order, thus giving rise to a potential 2.433x1018 (4.s.f) different combinations, and therefore interactions between the various amino acids.

Alzheimer’s: Scientists know that during Alzheimer’s two abnormal proteins build in the brain. They form clumps called either ‘plaques’ or ‘tangles’. These plaques and tangles interfere with how brain cells work and communicate with each other. The plaques are usually first seen in the area of the brain that makes new memories. A lot of research is focused on finding ways to stop these proteins in their tracks and protect brain cells from harm.

In the early stages of this disease Reagan stated; "I have begun the journey that will lead me into the sunset of my life." Research has been underway for years and years. One of the more promising avenues entertains the idea that these amyloid plaque proteins are the cause of changes in the brain. "The damage occurs when neurons congregate and form protein masses called amyloids that are water-soluble in normal brains but undergo structural changes and can't be dissolved in Alzheimer's patients. The masses disrupt nerve cell functions and begin to cause symptoms such as the loss of short-term memory. The deterioration of the brain is accompanied by a drop-off in the production of the neurotransmitter acetylcholine, which plays a key role in cognitive functioning" (p.444). I do believe that these amyloid plaques do play a role in the changes observed. These tangles and plaques are kind of the tell-tale sign that Alzheimer's is present. The missing piece to the puzzle is, What gets the ball rolling? What causes these changes to occur? I am confident that if we can find the answers to these questions, that we can find a cure.

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.

Proteins are primarily considered to have one primary function to serve its role in an organism, however studies have observed to have multiple functioning proteins known as moonlighting proteins (Khan et al. 2014). Moonlighting proteins along with primary functions, have secondary functions that are not related to the primary function and does not correlate to the primary or other functions (Khan et al. 2014). The multifunctional proteins play essential roles in carrying out biochemical functions which aids in the cell growth but are not caused by gene fusion and multiple RNA splice variants (Amblee et al. 2015). The discovery of moonlighting proteins was first discovered by Piatigorsky and Wistow while observing crystallins (Khan et al. 2014). Crystallins, are structural proteins that are found in the eye lens that exhibit enzymatic activity to make the lens itself (Khan et al. 2014). Crystallin has a primary function to help form the lens of the eye by acting as a structural protein (Amblee et al. 2015). Besides enzymatic activity, crystallin was observed in other mammals to have secondary functions such as metabolic functions which are helpful in prokaryotic (Khan et al 2014). Most moonlighting proteins are characterized as cytosolic enzymes and chaperons, or in other words helping proteins (Amblee et al 2015). The multifunctional proteins or moonlighting proteins can also be identified as receptors, channel proteins and ribosomal proteins (Khan et al. 2014). Due to the

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.

Proteins are polymeric chains that are built from monomers called amino acids. All structural and functional properties of proteins derive from the chemical properties of the polypeptide chain. There are four levels of protein structural organization: primary, secondary, tertiary, and quaternary. Primary structure is defined as the linear sequence of amino acids in a polypeptide chain. The secondary structure refers to certain regular geometric figures of the chain. Tertiary structure results from long-range contacts within the chain. The quaternary structure is the organization of protein subunits, or two or more independent polypeptide chains.

Alzheimer 's disease is a non curable progressive condition caused by the degeneration of neurons, the main cellular component of the central nervous system. This degeneration is believed to be caused by a build up and entanglement of the functional proteins within and around the neuron. However, the exact cause of neuron

The Functions of Proteins Introduction Protein accounts for about three-fourths of the dry matter in human tissues other than fat and bone. It is a major structural component of hair, skin, nails, connective tissues, and body organs. It is required for practically every essential function in the body. Proteins are made from the following elements; carbon, hydrogen, oxygen, nitrogen and often sulphur and phosphorus.

The Aβ plaques comprised of accumulated proteins that formed a β-sheet rich tertiary structure, promoting a self-assembling property and becoming cytotoxic. These resulting structures are very similar in from and function to amyloid fibrils. Though not the sole cause of the degeneration, this amyloid like structure is predicted to have a strong connection with the disease. Evidence has also been provided by this research group that these Aβ plaques have a highly similar de novo generation as many prion positive proteins. The Aβ aggregation begins with a seeding of misfolded proteins. In the case of Alzheimer’s disease these Aβ plaques spread through the brain’s tissue through axial propagation. This is shown when plaques are injected into a Aβ-rich brain and are seen to spread along the expected pathway of axons, from the hippocampus, to the hippocampal fissure, then the subpial zone. This research generated the conclusion that these Aβ plaques are essentially PrLPs. According to Walker the research also supports the designation that the seeds could be considered Aβ prions, as the molecular and protein properties of these match those given the yeast prions and other PrLP found throughout human disease.

The brains of people with Alzheimer’s disease have an abundance of two abnormal structures – amyloid plaques and neurofibrillary tangles. These are made of misfolded proteins which can stick together with other misfolded proteins to form insoluble aggregates. If these aggregates build up, they can disrupt cellular communication and metabolism. The third main feature of Alzheimer’s is the loss of connections between cells leading to the ill-functioning and death of cells (Institute and Aging, 2011).

Campbell and Farrell define proteins as polymers of amino acids that have been covalently joined through peptide bonds to form amino acid chains (61). A short amino acid chain comprising of thirty amino acids forms a peptide, and a longer chain of amino acids forms a polypeptide or a protein. Each of the amino acids making up a protein, has a fundamental design that comprises of a central carbon or alpha carbon that is bonded to a hydrogen element, an amino grouping, a carboxyl grouping, and a unique side chain or the R-group (Campbell and Farrell 61).

Proteins play a part in every cellular activity and must fold into proper three dimensional configurations, or native state, to execute their intended functions. Proteomic stressors such as chemical exposure or elevated temperature can inhibit protein folding upsetting protein homeostasis and resulting in cell death and human disease (Broadley 2009). Excessive protein misfolding can lead to amyloid fibrillar aggregates which deposit around brain neurons contributing to the development or progression of neurodegenerative disorders: Alzheimer’s disease, Huntington’s disease and Parkinson’s disease are all fundamentally diseases of protein misfolding (Soto 2003, Hartl 2009).