Large Animal Models For Neururodegenerative Diseases Case Study

There are 20,000 new cases of ALS diagnosed each year in the United States. This yields an incidence of 3 per 100,000 (Brown, 2006). There is no known cause for ALS in 95% of patients; however, 5% have an identifiable genetic mutation (Elman, 2016). The disease can present in individuals less than 30 years of age, but peaks between 40 and 60 years of age. Before the age of 65, more diagnoses are made in men; after the age of 65, gender incidence is equal. There is no clear-cut ethnic or racial predisposition in ALS (Ricks, 2016). The lifespan is approximately 3-4 years after diagnosis. However, in 10 % of

ALS, better known as Amyotrophic Lateral Sclerosis, is considered as a complex genetic disorder, in which multiple hereditary and environmental factors combine to cause this disease. This is seen as an illness of parts of the nervous system that control voluntary muscle movement. In ALS, the motor neurons (nerve cells that control muscle cells) are gradually lost. When these motor neurons turn out to be lost, the muscles they control become weak and ultimately nonfunctional. We see that “amyotrophic” is rooted in Greek origin meaning without nourishment to muscles and refers to the loss of signals nerve cells normally send to muscle cells. “Lateral” simply means to the side and refers to the location of the damage in the spinal cord. “Sclerosis” means hardened and refers to the toughened nature of the spinal cord in advanced ALS. This progressive neurodegenerative disease, that was first discovered 150 years ago, is associated with a life expectancy of approximately three years after symptom onset. In the United States, ALS is also known as Lou Gherig’s Disease, named after the Yankees Baseball player who passed away because of it in 1941. In the United Kingdom and other parts of the world, it’s often referred to as motor neuron disease in reference to the cells that are lost in the disorder (ALS Association, 2015).

Although it is not known how the SOD1 gene leads to ALS, there is increasing evidence that mutated SOD1 can become toxic. It was suggested that the changes in processing RNA molecules, the ones associated with gene regulation and activity, could be a factor to causing ALS, due to the discovery of certain genetic mutations, but it’s just a possibility. In 2011, there was a defect in the C9orf72 gene which was found in both ALS patients and some frontotemporal dementia patients, and suggests the genetic ties between both neurodegenerative disorders (Amyotrophic Lateral Sclerosis (ALS) Fact Sheet, 2016). Consequently, due to no concrete causes, there can be no definitive diagnosis. In order to detect ALS, a series of tests must be done, as it is diagnosed through the process of elimination. Some diagnostic testing includes an electromyography, which detects electrical activity in muscles. Magnetic resonance imaging (MRI) can also be done to show a detailed picture of the brain and spinal cord. A muscle and/or nerve sample from the body can be examined, as well as urine and blood

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. ALS causes muscle weakness and impacts physical functions this occurs in the nervous system. In the nervous system motor neurons of the body are being affected. Usually, ALS causes weakness and paralysis in the muscles. The muscles slowly waste away and a person’s legs and arms become much weaker. In some cases there may be muscle spasms, weight loss, and difficulty in breathing, eating, and swallowing. The mind does not get affected and there is no loss of sensation, or sense of touch during ALS. The average for a person with ALS is about two to five years from the time diagnosis. In some cases people can live with the disease for five years and more. ALS is mostly being develop between the ages of 40 and 70. Athletes usually get diagnosed between 30 and 34. It shows that athletes have had multiple head trauma and they also have abnormal

Amyotrophic Lateral Sclerosis, otherwise known as ALS or Lou Gherig’s disease, is a neurological disease which attacks nerve cells causing them to die and leave the muscles paralyzed. People with ALS lose strength and control of muscles, weakening them and causing them to start to wear away. Eventually the muscles stop working all together and cause paralysis in places such as arms, legs and other parts of the body. When the nerve cells in the diaphragm and chest wall are attacked and the muscles are paralyzed, the person can lose the ability to breathe without assistance, or sometimes at all. Respiratory failure is the cause of death for most people with ALS. Currently there are approximately 2500-3000 Canadians that are living with ALS and according to www.als.ca “Every day two or three Canadians die of the

ALS is one of the most common neuromuscular diseases worldwide (Amyotrophic Lateral Sclerosis Fact Sheet).There are three different types of ALS causes there is, familial, sporadic, and guamanian. Familial is 5-10% , sporadic is the most common which is 90-95% of all ALS causes and guamanian is rare variant. Guamanian is very similar to ALS almost the same and it happens because of something toxic that they are eating which messes with their nervous system (ALS[Lou Gehrig’s Disease]). It is also a disease varied with etiology characterized by rapidly progressive in weakness in the muscles.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord (Plowman, 2015, p.1151). The motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles in the body. When ALS is in a degenerate stage, this causes paralyzation and loss of muscle control, which can lead to one’s death. The ALS Association is a national nonprofit organization that is dedicated to fighting Lou Gehrig’s disease by providing support and information to those that have this disease, as well as spreading awareness effective for change. The ALS Association aims to discover new treatment for those living with Lou Gehrig’s disease, while actively seeking a cure

Genetic factors not only affect the familial cases, but they also are likely to play a role in some of 4 the sporadic cases.9 Among the familial cases about 200/s 3'12 contain causative genetic lesions in copper-zinc superoxide dismutase (SOD 1). 3'7 ALS could be an oxidative neurotoxicity brought on by this mutation in the SOD 1 protein:1'11 A leading hypothesis of the development of ALS is /glutamate excitotoxicity.1°'12 Concepts of excitotoxicity may help explain the selective neuronal death that occurs.10 Excitatory neurotransmitters, such as glutamate, can damage postsynaptic cells with excess concentrations.I° Glutamate levels are elevated in serum, spinal fluid, and brain tissue of ALS patients.11'12 It is also hypothesized that deficiency of nerve growth factor may cause ALS.II Neurotrophic growth factors might rescue the cells that are destroyed in ALS.I "12 Additional cause for ALS may be derivative of industrial pollutants and occupational exposure to chemicals associated with welding and soldering." Symptoms ALS is characterized by a combination of both upper and lower motor neuron ✓ symptoms9'I2 that lead to respiratory insufficiency within a few years.1° Lower motor neuron symptoms include weakness, muscle wasting, hyporefexia, muscle cramps, and fasciculations.9'11 Spasticity, hyperreflexia, Hoffmann sign, extensor plantar responses, hyperactive jerk and gag reflex,

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease (ALS Association, 2016). A neurodegenerative disease is a disease in which nerve cells are damaged or killed. In this particular case, the damaged motor neurons affect voluntary movements (Newton et al., 2000). Amyotrophic lateral sclerosis, commonly known as ALS for short, got its name from the Greek language. By breaking the name into a-myo-trophic; “a” means no, “myo” refers to the muscle cells, and “trophic” refers to nourishment (ALS Association, 2016; Gulli & Veillette, 2002; Hains, 2006). “Lateral” indicates the area of the spinal cord where the nerves are being affected (Gulli & Veillette, 2002). “Sclerosis” refers to the scarring and hardening of the spinal cord

There are several factors being explored as potential causes. Because there are familial cases of ALS, gene-related causes are worthy of investigation with the SOD1 (copper-zinc superoxide dismutase) gene being one of greater interest. Mutations in the SOD1 gene have been found in a fifth of familial cases of ALS (Rosen). Mutations to this gene, rather than having a detrimental effect on its own antioxidant enzyme function, appear to cause disease through toxic gain (Shaw). Oxidative stress and increase in reactive oxygen species can cause cell death, and because mutations in the SOD1 gene can allow this to occur, it could be a potential mechanism for ALS neural degeneration (Wijesk).

ALS, also known as Lou Gehrig’s Disease, is a progressive neurodegenerative disease. The nerve cells of the brain and spinal cord stop functioning properly, leading to malnourished muscles, muscle atrophy, loss of motor function, and eventually death (ALS Association, 2016). ALS stands for amyotrophic lateral sclerosis, which basically means “no muscle nourishment” in the lateral aspects of the spine where some nerve cells that control the muscles are located (ALS Association, 2016).

ALS, or amyotrophic lateral sclerosis, is a disease that damages motor neurons in the brain and spinal cord. It is a deadly disease that cripples its victims due to breakdown in the body’s motor neurons. Motor neurons are nerve cells that control muscle movement. They are important part of the body’s neuromuscular system. The neuromuscular system allows our bodies to move and is made up of the brain, many nerves, and muscles. People that are diagnose with ALS disease causes for the motor neurons in the brain and the spinal cord to shrink and disappear, so that the muscles no longer receive signals to move eventually causing the muscles to become smaller and weaker. Slowly the body becomes paralyzed, which means that the muscles no longer function. The average life expectancy for a person that has ALS after being

The effects that ALS (Amyotrophic Lateral Sclerosis) has on the human body at the cellular level are trademarks of the disease and can be attributed in a large part to genetic mutations causing these phenotypes. ALS is autosomal dominant, meaning that if one parent has a gene that causes ALS, there is a 50% chance that one of their offspring may also have one of the genes that causes ALS. Men are slightly more likely to get ALS at a younger age than women are at a younger age but this gap begins to dwindle as the ages of people with ALS increases. Despite the fact that many genes have been discovered that cause ALS, a large portion of genes and mutations have yet to be found. The two groups of ALS, familial and sporadic, both have genetics

Only an estimated 2-7% of ALS causes are a result of genetic mutations of TDP-43 (Dekker et al., 2016; Hayashi et al. 2016). However, approximately 97% of ALS and 45% of FTLD patients have misfolded TDP-43 aggregates absent of mutation (Bozzo et al., 2016). This confirms that a mutation in the TDP-43 gene is not necessary for the generation of TDP-43 aggregates. SOD1, TARDBP, FUS and C9ORF72 were identified in approximately 7% of sporadic ALS patients with C9ORF72 being the most frequent (Dekker et al., 2016). Studies have indicated that mutant TDP-43’s resistance to degradation is linked with its primary mutation (Scotter et al., 2014). SOD1 mutations have also shown to inhibit UPS functionality (Keskin et al., 2016). Remarkably, no

A distinctive characteristic of ALS is that although the motor neurons die, the brain, cognitive functions and sensory neurons stay intact (Porth & Matfin, 2009). This makes the disease especially devastating because patients become trapped inside their dying body, with a fully alert mind, but are unable to move. It is not known what causes the exact death of the motor neurons in the body, but “five percent to 10% of cases are familial; the others are believed to be sporadic” (Porth & Matfin, 2009, p.