Amyotrophic Lateral Sclerosis: Lou Gehrig's Disease

Amyotrophic Lateral Sclerosis

A Look at ALS

Amyotrophic Lateral Sclerosis, or ALS, is a neurological disease that disrupts the functioning of motor neurons in the afflicted person. Commonly known as Lou Gehrig’s disease in the US, developing the disease usually guarantees that a premature death is unavoidable. ALS is a degenerative disease, which means nerve cells deteriorate, but all neurological disorders involve the exacerbation of neuron functioning, so what sets ALS apart from other neurological diseases? According to the National Institute of Neurological Disorders and Stroke (NINDS 2013), typical ALS patients are characterized by the steady failure and decline of functioning motor neurons. A common and fit person unaffiliated by ALS

would have no problem talking clearly, exercising, or simply moving their arms or legs at will. Victims of this neuromuscular disease lose these overlooked abilities before eventually dying within 10 years; most victims do not make it past the five-year mark. The prevalence in the US is 3.9 cases per 100,000 persons, and more than 12,000 people have a definite case, so ALS is a relatively common disease across the nation (NINDS, 2013). This life-changing disease has no definite cure, but researchers have made progress in the improvement of managing the ill-fated people that develop the disease.
Signs of the deadly disease are usually clear as day. Moreover, a red flag signaling that someone has ALS is that everyday tasks like walking the dog or simply washing themselves become daunting tasks for the person. As ALS progresses, numerous abilities are lost; walking, dressing, writing, speaking, swallowing, or even breathing can be lost, resulting in a depleted life span (ALS Association, 2016). A crippling predicament without a doubt, but what is the underlying cause of these severe disabilities? Motor neurons, or nerve cells that control muscles, are a crucial part of working and moving the muscles of the body around effectively, but it depends on which muscle neurons that are decaying earliest. Experts have put forward that the neurons located in the spinal cord, called lower motor neurons, control the limbs, arms, chest, breathing, and facial muscles, whereas the upper motor neurons of the cerebral and motor cortexes solely regulate the motor cells of the brain (Kandel, 2012). In a normal case, lower motor neurons will send and relay the message from the upper motor neuron and produce a muscle contraction thereby moving the corresponding joint, producing a simple movement. An implication of ALS is evident when the connection between upper and lower motor neurons is lost. This can be frustrating, as control over hands, standing, or even eating a meal will vanish as time goes on. To make matters worse, the decisive factor of ALS is that losing the ability to breathe will lead their untimely demise. In other words, ALS progressively kills the neurons responsible for sending messages to contract muscles, causing the loss of the brain’s control over crucial movements like breathing or swallowing.
ALS affects various parts of the central nervous system, but researchers have found that certain key areas are primarily affected.

Primarily the basic functioning of the cell influences the development of the disease. Cells must be able to transport materials and messages from all over the body, and along a motor neuron’s axon in order to preserve the life of a nerve cell, but research suggests that the motor neurons can be vulnerable to any defect that might hinder axon transport. Apoptosis, or the systematic process of cell death, in which cells receive insufficient amounts of materials, has been a part of designing effective treatments for ALS, as it is at the core of the disease. Apoptosis is a normal physiologic occurrence; actually, being regarded as a central part of the nervous system’s growth (ALS Association, 2016). If there is a case of extreme apoptosis, problems may arise. Alternatively, while apoptosis might be part of the development of the nervous system, necrosis results from a direct injury or infection to the nervous system. The process of necrosis involves an explosion of the cellular content, creating a mess of

inflammation.
Consequently, the mitochondria is an additional piece of the cellular equation and is one more part of the cell that is involved in the onset of ALS. The power core of the nerve cells, the mitochondria must endure the cell’s energy from all around the body. Additionally, the mitochondria is responsible for the cellular content of calcium ions. Calcium is essential to produce signals that contract muscles, produce thoughts and has control over delaying or stimulating specialized enzymes. Evidence has revealed that even before a physical change like limb weakness in mice, changes in the mitochondria can be observed (ALS Association, 2016). Thus, researchers are studying this area of the cell extensively, and further findings concur that damage to the mitochondria might occur early in the progression of ALS. The indication is that calcium entry causes the release of pro-apoptotic proteins and activation of enzymes involved in apoptotic pathways (Jaiswal, 2013). They also recorded the importance of mitochondrial dysfunction and calcium homeostasis, stating that when motor neuron’s large amount of voltage and ligand gated calcium channels are activated, calcium rapidly floods the cell, resulting in mitochondrial calcium overload. Therefore, the pathogenesis of ALS might involve the extended depolarization of the cell (due to calcium overflow), which leads to excessive apoptosis, solely in the motor neurons.
While it may seem that ALS only affects the use of muscles, contrasting studies have displayed otherwise. Examined during were the diminishing symptoms unrelated to motor functioning, including executive and memory discrepancies (Raaphorst, 2015). Memory of language was frequently found to be associated with the volume of the hippocampus in ALS patients, suggesting that the hippocampus might be involved in the cognitive impairment portion of ALS.
Like any other functioning system, the human body needs to transmit messages all over the body and do it swiftly.

Neurotransmitters, like glutamate, are messengers that pass signals from one neuron to another, thereby communicating to receiving neurons whether to fire off its own neurotransmitters, or not. If a neuron has a prolonged excitatory period from excessive glutamate, the results can be lethal (ALS Association, 2016). Glutamate, an excitatory neurotransmitter, becomes harmful when neuron’s messages become unusual and overwhelming e.g. in the case of a stroke. Responsibility of concentrating glutamate equally around the neurons falls to molecules called transporters. When it is not properly concentrated and causing an overflow of excitatory responses, glutamate is an issue. Nevertheless, excessive glutamate can be problematic in ALS patients and treatment involves being able to deliver glutamate transporters to ALS affected

cells.
The vast majority of ALS cases are sporadic or have unknown causes, implying that professionals are merely chipping away at the tip of the iceberg when attempting to resolve the disease. Looking at the bright side, studies have shown that only 5-10% of cases have genetic mutation, meaning a small percentage of cases are hereditary (ALS Association, 2016). Mutations occur when there is an error in DNA, causing a cell to alter its functioning. For example, when the superoxide dismutase (SOD1) protein mutates, it gains a different and toxic function that causes ALS. These mutations are harmful because of their effect on a specific type of RNA, the gene and protein messenger, mRNA. Copies of the mRNA are used to guide the formation of the protein, which then has to be processed. However, during this complex process, mistakes might occur, resulting in a case of ALS. Oddly enough, there are small differences when considering cases of ALS with a family history or no family history, leading experts to conclude that understanding gained from sporadic cases might benefit even those people that inherit the disease.
Resolving ALS
Living with ALS is no walk in the park. Researchers have conducted numerous studies in the search for some sort of answer to the neurodegenerative disease. The claims that the first drug treatment for ALS, Rilutek, reduces damage to motor neurons through inhibiting the release of glutamate (NINDS, 2013). Prolonged survival is the extent of the drug’s use, but keeping an ALS patient moving comfortably before they are completely immobilized, is the aim of overall treatment. Accordingly, while studies have shown a glimpse of hope for ALS patients, curing the disease is far off, yet determining innovative approaches to inhibit glutamate and increase longevity of patients with ALS is at the forefront of research.