Amyotrophic lateral sclerosis (ALS) presents as progressive weakening of all the voluntary muscles in the body due to the degradation of motor neurons. It is a severe motor neuron disease (MND) that is usually fatal within 5 years due to arrest of the respiratory muscles [Rowland, 2000]. It is only relatively recently that studies have defined specific gene mutations affecting protein function, giving some hope for finding an effective therapy for ALS. Currently there is no cure or treatment for the disease. Over the last five years discovery of mutations in two genes, transactive response (TAR) DNA-binding protein (TDP-43), so called because of its 43-kDa mass, and fused in sarcoma/transloacted in liposarcoma (FUS/TLS) have shifted research into trying to understand the roles of RNA metabolism in neurodegeneration. This micro-review will try to summarise what is known so far about TDP-43 and FUS/TLS and how they relate to pathogensis of ALS.
TDP-43 was first identified in 2006 [Neumann, Sampathu and Kwong, et al., 2006] where it was shown there was a link between the protein and both ALS and frontotemperal lobar degeneration (FTLD). This study used double-labelling immunofluorescence to show that TDP-43 antibodies (antiTDP-43) immunolabelled ubiquitinated cytoplasmic, nuclear, and neuritic inclusions in sALS. However, it remained unclear how and what gene mutations were the underlying cause. This study observed that patients with ALS and FTLD had pathologic TDP-43. It
Amyotrophic meaning, “no muscle nourishment” in Greek, lateral meaning where the neurons are in the spinal cord, and sclerosis meaning “scarring.” ALS, often known as “Lou Gehrig’s Disease,” named after the New York Yankee who first brought awareness to the disease in the late 1930’s, is a neurodegenerative disease, which affects the neurons in the brain. The nerve cells in the brain and spinal cord that are responsible for sending and receiving motor signals progressively die off, causing the deterioration of simple motor skills in patients with ALS, such as walking, talking, and eventually speaking and breathing, however thinking is not affected by ALS. Early symptoms cause the person to slowly lose mobility of limbs, but in a matter of a few years, the person loses the mobility of most of their body and will eventually lose the ability to eat and breath, which will ultimately cause death. ALS deteriorates the patient's body, however does not affect the patient's state of mind or sanity while the rest of the body shuts down. People usually get ALS between the ages of 40 and 70. However, there is a growing trend where athletes are getting ALS in their thirties. ALS can be contributed to genetic predisposition, which means that the gene that is responsible for ALS is already in the person’s DNA. In recent studies, however, it was observed that individuals who have had suffered multiple concussions or any other head trauma are
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a terminal disease that degenerates the nerves in the brain and spinal cord. Motor neurons run from the brain, through the spinal cord, and into the muscles of person; this is what allows a person to have control over voluntary movement. When an individual is diagnosed with ALS, their motor neurons begin to degenerate, thus eradicating their ability to walk, eat, and eventually breathe.
ALS is more commonly known as Lou Gehrigs disease. The progressive disease poisons the nervous system by a chemical that is released after a blow to the head; this chemical is known as Tou. Tou is released into the brain after a blow, poisoning the nervous system causing body muscles to shut down.
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
“A-myo-trophic comes from the Greek language ‘A’ meaning no or negative. ‘Myo’ refers to muscle, and “Trophic” means nourishment-’No muscle nourishment’... ‘Lateral’ identifies the areas in a person's spinal cord where portions of the nerve cells that signal and control the muscles are located.” (“What is ALS?”). Literally, Amyotrophic lateral sclerosis means no muscle nourishment in the spine. In this disease, nerve cells in both the brain and spinal cord slowly die over a period of time. The cells, referred to as motor neurons, control the muscles throughout the body, resulting in death or paralyzation as they degenerate. At any given time, ALS can strike anyone. It is not contagious, however, in about 10% of cases, ALS runs in the family making it somewhat hereditary (“What is amyotrophic lateral sclerosis?”). “The incidence of ALS is two per 100,000 people” (“Facts You Should Know). Most of the time, Lou Gehrig’s disease (ALS), acts on middle-aged and older adults, however there have been noted cases of patients much younger. Considering that a friend or family member can be diagnosed with this horrible disease, everyone should pitch into ALS charities in hope to find a
Amyotrophic Lateral Sclerosis was discovered in 1869 by a French neurologist named Jean-Martin Charcot. However, the disease did not become known worldwide until 1939 when famous baseball player, Lou Gehrig was diagnosed. The disease later took his life. Amyotrophic Lateral Sclerosis, also known as ALS, or more commonly known as Lou Gehrig's disease, is a progressive neurodegenerative disease that attacks nerve cells in the brain and the spinal cord. Motor neurons extend from the brain to the spinal cord and from the spinal cord to the muscles distributed throughout the human body. Degeneration of motor neurons eventually lead to death. Amyotrophic comes from the Greek language which translate into "No muscle nourishment. ALS can be summed
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 (ALS) or Lou Gehrig’s disease is a progressive nervous system disease. It constantly destroys the neurons responsible for muscle movements, especially the lower and upper motor neurons. ALS affects the nerves in your brain and spinal cord that controls your muscles. The nerves that are affected eventually break down and disappear. It got the name Lou Gehrig’s disease because of the famous baseball player, Lou Gehrig who died of ALS.
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
There are many known diseases in the world that we live in today affecting a wide range of individuals of different ages, ethnicities, and genders. With each type of disease comes a diagnosis, prognosis, and potential for a cure from one of life’s many ailments. Over the course of time, technology has began to lead the way in discovering as well as treating many disease in which doctors previously knew little about. Amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig’s disease, was first described in 1869 by French neurologist Jean-Martin Charcot. In 1939 ALS brought international attention when Lou Gehrig abruptly retired from baseball after being diagnosed with the disease(6).
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
ALS is considered a neurodegenerative disease because it kills neurons, specifically, motor neurons. These neurons reach from the brain to the spinal cord, and from the spinal cord to muscles throughout the body. Motor neurons provide muscle control and voluntary movements such as reaching for something, or bending your knee. When a person has ALS, these neurons become damaged and can eventually die. The death of motor neurons causes the brain to lose control over movement of muscles. People with
Summarizing the presented information, all the mentioned methods have added each other enriching the knowledge about the factors resulting in ALS. A factor of crucial importance is that all the methods allowed examining the pathology of ALS in vivo. Furthermore, studies in vivo have been approved boosting the detection of ALS at very early stages including genetic prognoses in the pre-symptomatic stage of the disorder. Thus, combining various methods of medical investigation offers the best opportunities for exploring the pathology of
ALS and FTD were traditionally considered as two completely different neurological disorders with distinct clinical features. ALS was first defined as a pure motor neuron disease in which both upper and lower motor neuron degenerates. It has now been established that ALS and FTLD can co-occur in the same individual. About 50% of ALS patients show some degree of cognitive impairment and at the other end of spectrum, around 40% of FTLD cases have measurable motor dysfunctions. The concept that ALS and FTLD represent two end of same disease spectrum was further supported by neuropathological evidence concerning the abnormal protein aggregates observed in degenerating neurons. Initially, immunoreactive, ubiquitin-positive neuronal inclusions were
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.