Amyotrophic lateral sclerosis (ALS)
It is not surprised that one of the common progressive motor neuronal disease, ALS, is also genetically connected to the mutations of degradation machineries with varied etiology. Even the majority of ALS is sporadic, two of familial ALS is mainly associated with simple monogenic factors, the mutation of SOD (D90A) and a large hexanucleotide (GGGGCC) repeat expansion in chromosome 9 open reading frame 72 (C9ORF72). However, growing evidence of genetic mutations in proteostasis factors discovered in familial ALS such as, UBQLN2, VCP/CDC48 in the UPS and SQSTM1/p62, VAPB and some of the vesicular traffic proteins in autophagy have been suggesting a fragile capacity of proteostasis in vulnerable neurons (Bedford et al., 2008; Deng et al., 2011; Paine et al., 2013; Johnson et al., 2010).
Recent genetic and biochemical study revealed that mutations in a unique PXX repeat region of UBQLN2 which is one of ubiquitin like protein family are causative in ALS. The different mutations of UBQLN2 are present in the typical skein-like inclusion which is a hallmark of ALS pathology. In detailed functional relevance of ubiquitin like domain (UBL) and ubiquitin association domain (UBA) of UBQLN2 still need further elucidation, degradation of UPS reporter slowed in neuroblastoma cells transfected with mutations of UBQLN2 (Deng et al., 2011). Interaction of another member of the ubiquilin family (UBQLN1) with polyubiquitylated TAR DNA-binding protein 43 (TDP43) which is also genetically linked to ALS may imply fundamental functions of ubiquilin family in ALS pathology (Kim et al., 2009).
Another evidence of linkage between ALS and the UPS component came from the identification of mutations in valosin contai...
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...ernatively, loss of VAPB functions in VAPB mutations linked to ALS has been suggested by a resent genetic study using zebra fish and mice models. Thus, knockdown of VAPB in zebra fish was causative to swimming deficits and knockout of VAPB in mice led mild motor deficits (Kabashi et al., 2013). Presumably, arising number of different positional mutations at VAPB linked to sporadic ALS might indicate susceptibility of neuronal weakness increased in losing of its native function (Ingre et al., 2013).
Aging / HSF1 / UPR (Ben-Zvi et al., 2009; Cohen et al., 2012; Denny et al., 2013)
Although numerous stress conditions lead to an imbalance of proteostasis, aging is the most deleterious risk factor for the onset of protein aggregation diseases. The declined activity or inefficient assembly of the proteasome in aging process exacerbate collapsing of proteostasis further.
On December 1, 2012, a patient by the name of John Dough walks into the medical assistant’s office. The patient is five foot 11 inches tall, currently he is 70 years old and weighs approximately 211 pounds. The patient has no known allergies does not smoke and has a relatively clean health record. After filling out the patient medical history forms, the patient is seen by the doctor. The patient explains to the doctor that lately he has had trouble lifting object he would not normally have trouble with, as well as walking short distances, and being very fatigued. After further examination the patient explains how he recently found a tick on his back and removed it, but now there is a red bullseye on his back. The physician suggests a blood sample be taken and sent to the laboratory. To help with weakness and fatigue he recommends the patient to get a good nights sleep and drink plenty of fluids to avoid dehydration. He also wants the patient to limit medication intake that could contribute to fatigue such as cold and allergy medicines and make sure to finish all daily exercising three to four hours before bed. The patient schedules a check up two weeks later.
Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Amyotrophic Lateral Sclerosis is better known as ALS or Lou Gehrig’s disease. Amyotrophic Lateral Sclerosis was not brought to International or national attention until Famous New York Yankees baseball player, Lou Gehrig, was diagnosed with it in 1939. Jon Stone, the writer and creator of Sesame Street, was also diagnosed with Amyotrophic Lateral Sclerosis. Amyotrophic Lateral Sclerosis is very deadly and it physically handicaps a person as it progresses. There are two types of Amyotrophic Lateral Sclerosis, Sporadic and Familial. Sporadic is the most common cause in some cases and Familial is inherited, which is rare. Amyotrophic Lateral Sclerosis is one of the most aggressive muscular atrophy disorders, it has many signs and symptoms, and it can be treated but cannot be cured.
Neurodegeneration is used mainly for diseases that are characterised by progressive loss of structure and function of neurons. There are many neurodegenerative diseases including amyotrophic lateral sclerosis that...
Kellermann, A., & Peleg, K. (2013, May 29). The New England journal of medicine. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMp1305304
TSEs or more commonly prion diseases are a group of invariably fatal neurodegenerative diseases that occur in humans and animals . This disease is caused by a protease –resistant protein (PrPsc) after misfolding of a host-encoded prion protein (PrP). TSEs can exist as genetic, infectious or sporadic forms. The diseases are characterized by dementia, ataxia and neuropathlogically due to loss of specific neurons in the brain. Other clinical features include persistent painful stimuli, dystonia, visual or cerebellar problems and gliosis (1).
have been cases of ALS linked with the mutation in the gene that produces SOD1
National Institute on Aging. (n.d.). National Institute on Aging. Retrieved September 19, 2011, from http://www.nia.nih.gov
In this essay, the disease Multiple Sclerosis (MS) will be reviewed. This piece of work will lay emphasis on the pathophysiological, psychosocial, economic and cognitive effects it has on the individual, family and society. It will also make mention of how a professional nurse would support the individual, the family/carer, the nursing process and the professional role of the nurse according to the Nursing and Midwifery Council (NMC) code of conduct which sets a standard for all nurses and midwives (NMC, 2008) . It has been chosen because this chronic disorder is quite prevalent in the UK.
Where and how this deadly disease originated is unknown, but it was first identified in 1869, by the noted French neurologist Jean-Martin Charcot. ALS is not contagious, but research is still vague on the cause of the disease. Today, there are three recognized forms of ALS: genetic, sporadic, and Guamanian. The genetic form of ALS appears to be inherited or passed down within a family, and about ten percent of ALS patients have a family history of the disease. An abnormal gene has been located in about half these families, but the cause of the remaining half is still unknown. The next, most common form, is sporadic ALS. These patients have no family history of disease, and the cause of their coming down with ALS is a mystery. Finally, is Guamanian ALS, called this because a high percentage of cases occur in the Pacific Islands near Guam.
Oeseburg, H., de Boer, R.,A., van Gilst, W.,H., & van, d. H. (2010). Telomere biology in healthy aging and disease. Pflügers Archiv - European Journal of Physiology, 459(2), 259-68. doi:http://dx.doi.org/10.1007/s00424-009-0728-1
Imagine if you loss control of your body but your mind stayed unaffected. You would be a prisoner in your own body, all leading up to your death sentence. That is the sad fate for the people diagnosed with Amyotrophic lateral sclerosis (ALS). “Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder was first described by Ran in 1850. This description was then expanded in 1873 by Charcot, who emphasized the involvement of the corticospinal tracts. In the United States, ALS is often referred to as Lou Gehrig's disease, after the famous ball player who was stricken by the disease in the midst of his career. (Yale School of Medicine, 2014)” In this paper will go through the definition, the process, the signs, the risk factors, etiology, and discus the known people that have suffered with this terminal disease.
Aging affects all living organisms, which is characterized by the loss of cellular homeostasis causing systemic cellular dysfunction. In fact, both the mitochondrion and the actin cytoskeleton show age-associated declines in functions. As an organism age, mitochondria accumulate mtDNA mutations, which result in mitochondrial dysfunction. The actin cytoskeleton also declines with age. This affects establishment and maintenance of cell polarity as well as cellular and intracellular movement, which in turn contributes to age-associated declines in systems including the immune system and skeletal muscle. In addition, many age-related pathologies like neurodegenerative diseases, such as Alzheimer’s, display dysfunction in mitochondria and actin. Interestingly, Dr. Liza Pon’s
Elderly, 1991. American Journal of Public Health, 84(8), 1265. Retrieved from Academic Search Complete database.
Neurodegenerative diseases are characterized by the presence of protein aggregations with a varying protein content depending on the type of disease formed. One of the prime diseases resulting from protein inclusion bodies (aggregations) is Amyotrophic Lateral Sclerosis (ALS), which was the broad scheme of focus throughout this study (NIH 2017). ALS is a fatal neurodegenerative disease that causes death of motor neurons in the motor cortex, brainstem and spinal cord, as well as peripheral skeletal muscles (first in the limbs, then progressively beyond those distal extremities). This leads to motor problems, muscle weakness, and paralysis. These motor impairments are gradually progressive, and therefore ALS is usually fatal within 3–5 years
This is a neurodegenerative disease, meaning it results in progressive loss or death of neurons. It often starts off with effecting simple motor skills like writing and holding things, after a few months usually patients start losing the ability to walk, talk, or move any of their limbs. Although the brain trauma is what causes it, ALS has little-no-effect on the brain. This fatal disease is typically diagnosed around age 60 and most patients are given about 3-5 years to live after being diagnosed. It has been found that 10% of cases are shown as genetic. It was brought to attention that athletes were beginning to get diagnosed with ALS at a younger age than most. After extensive research in the early 2000’s, Brain Analyst, Dr. Mckee ran tests and finally came to the conclusion that the toxic proteins in the brains of ALS patients were coming from repeated blows to the head. It was then made evident why so many athletes in contact sports such as football, soccer, boxing, etc… were being diagnosed at such a young age and more frequently than