ALS (Lou Gehrig's Disease)
Video describing ALS and the history behind ALS being called Lou Gehrig's disease [3]

Amyotrophic Lateral Sclerosis(ALS) is a progressive neurodegenerative disease which targets upper and lower motor neurons. As the disease progresses there is muscle weakness and atrophy, which result in the loss of bodily functions such as dysarthria, dysphagia, dyspnea. The disease progresses into the lethal stage when the patient can no longer breathe [1]. The most common mutation found in ALS patients is superoxide dismutase 1 (SOD1), which is characterized by rapid progression and death [2]. Studies on SOD1 ALS1 mice demonstrate that there is extensive degeneration of gray matter oligodendrocytes, and that the removal of this mutant delays the disease onset and extends survival in ALS mice. Currently Riluzole is the only FDA approved drug used to treat ALS, and it only prolongs the average lifetime of an ALS patient by 2-3 months. There are currently different therapies being researched, including using various stem cells to re-grow degenerated motor neurons, as well as preventative therapy to postpone degeneration of motor neurons [1].

1. Gordon, Paul. Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management, and Therapeutic Trials. Aging and Disease. (2013) 4(5):295-310
2. Chen S, Sayana P, Zhang X, Le W. Genetics of amyotrophic lateral sclerosis: an update. Mol Neurodegener. (2013) 8(28).

Diagnosis of ALS

main article: Diagnosis of ALS
author: Clara De La Pava

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Many advances in the research field aim towards finding an effective diagnostic method for ALS.

1. Introduction
Amyotrophic lateral sclerosis or Lou Gehrig ’s disease is a neurodegenerative disorder that affects the motor system in affected individuals. Its symptoms include muscle weakness, spasms and atrophy amongst others and patients generally begin displaying these between the ages of 40 – 65 or so. ALS progresses quite rapidly: about half of all diagnosed patients die about 30 months after symptoms first begin manifesting[1]. Because of this, it is crucial that individuals are diagnosed in the early stages so that proper care and treatment can be provided. In the present time, there is no specific test or examination that will guarantee a definite diagnosis; however, medical practitioners rely on a set of certain characteristics or signs to reach an accurate diagnosis[1]. There is no single test that will diagnose an individual with ALS; however, there are many different characteristics of this disease that can be identified using tests and therefore point practitioners in the right direction. El Escorial Criteria in particular mentions the specific characteristics and features that need to be displayed in an individual for a proper ALS diagnosis[1]; although they are not exclusive. It classifies diagnosis into four different categories depending on severity of upper as well as lower motor neuron degeneration (which must not be explained by the presence another neurological disorder)[1]. Physicians use a combination of a few methods such as electromyography and neuroimaging[2],[3] to identify UMN and LMN which is the most prominent feature in neurodegenerative disorders and therefore ALS. Furthermore, current research is looking into whole-brain magnetic resonance spectroscopic imaging (MRSI) as a source of determining disability levels in ALS in the future[4].

1. Kiernan, M., Vuvic, S., Cheah, B., Turner, M., Eisen, A., Hardiman, O., Burrell, J. & Zoing, M. Amyotrophic Lateral Sclerosis. Lancet 377, 942-955 (2011).
2. Krarup, C. Lower motor neuron involvement examined by quantitative electromyography in amyotrophic lateral sclerosis. Clin Neur 122, 414-422 (2011).
3. de Carvalho, M., & Swash, M. Sensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: A six‐month longitudinal study. Muscle & nerve 41, 208-211 (2010).
4. Stagg, C., Knight, S., Talbot, K., Jenkinson, M., Maudsley, A. & Turner, M. Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS. Neurology 80, 610- 615 (2013).

Genetics of ALS

main article: Genetics of ALS
author: Seiya Ishikura
Although familial amyotrophic lateral sclerosis (ALS) cases are present at only 10% of all ALS cases, knowing the underlying genes of those cases and the mechanisms of the mutations that lead to ALS can be of great help in determining how the disease works, even outside of those familial cases.[1] The SOD1 gene has been known for a long time as a gene present in many cases of familial ALS, however, the mechanisms explaining how SOD1 mutations aggravate neuron degeneration are unknown. It is thought that SOD1 mutations can have a variety of effects that result in neuron degeneration such as protein aggregation and oxidative stress.[1] The ALS2 gene and alsin protein have a role in protecting motor neurons, and can even suppress the activities of SOD1 mutations. Mutations in ALS2, like SOD1 mutations do not lead to full blown ALS but rather result in predictable muscular atrophy, and as such are good models of ALS.[2] TBD-43 is another gene that when mutated leads to protein aggregates, that can be seen in both FALS as well as SALS (sporadic ALS) cases. Work in the genetically linked ALS cases could be crucial to the discovery of the mechanisms that cause protein aggregation, and could lead to the discovery of drugs that can prevent protein aggregation and in turn could remedy victims of ALS.

1. Saccon, R et al. Is SOD1 loss of function involved in amyotrophic lateral sclerosis? Brain. (2013) 138(8) 2342-2358.
2. Gros Luis, F et al. Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish. Human Molecular Genetics. (2008) 17(17) 2691-2702.

Oligodendrocytes in Amyotrophic Lateral Sclerosis

main article: Oligodendrocytes in Amyotrophic Lateral Sclerosis
author: Andrea Velecela

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An oligodendrocyte wrapping three different neuronal axons

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease which causes death of upper and lower motor neurons, leading to a progressive loss of motor functions [Bibliography item Philips not found.]. The degeneration of motor neurons has been linked with the dysfunction of neuroglial cells such as oligodendrocytes. Oligodendrocytes main function is to provide support and insulation to the axons in the central nervous system (CNS), by creating the myelin sheat. They have been found to provide metabolic support to the neurons by supplying energy metabolites such as glucose and lactate [1]. Since the most abundant transporter of lactate in oligodendrocytes is monocarboxylate transporter 1 (MCT1), their disruption results in axonal damage and therefore neural loss. It has been found that oligodendrocyte progenitors (NG2+ cells) have an enhanced proliferation and differentiation, but even though new oligodendrocytes are being formed, they fail to mature, resulting in a progressive demyelination of axons. Experiments in mouse models in which the mutated gene that results in ALS, SOD1 (G37R) was selectively removed, lead to a delay in the disease onset and increased the survival of mice. This proposes that mutations are sufficient to produce death of motor neurons [2].

: Philips :Philips T, Bento-Abreu A, Nonneman A, Haeck W, Staats K, Geelen V, Hersmus N, Kusters B, Van Den Bosch L, Van Damme P, Richardson W, Robberecht W. Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis. Brain. (2013); 136: 471-482.
1. Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, Liu Y, Tsingalia A, Jin L, Zhang P, Pellerin L, Magistretti PJ, Rothstein JD. Oligodendroglia metabolically support axons and contribute neurodegeneration. Nature. (2012); 487: 433-448.
2. Kang SH, Li Y, Fukaya M, Lorenzini I, Cleveland DW, Ostrow LW, Rothstein JD, Bergles DE. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nature Neuroscience (2013); 16 (5): 571-579.

Therapy and Management of ALS

main article: Therapy and Management of ALS
author: Maxim Kashin

Amyotrophic Lateral Sclerosis (ALS)
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Description of the pathological causes and effects in ALS [1]

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that is characterized by the degradation of motor neurons throughout the affected person’s body. The degradation of the motor neurons causes muscular atrophy which ultimately results in the loss of function in muscles. The disease becomes fatal when the afflicted can no longer breathe due to muscular atrophy of respiratory muscles. Currently there is no known treatment that cures ALS, and there is only one FDA approved drug, Riluzole, that is used to treat ALS patients. Riluzole is a glutamate antagonist, which prevents the excitotoxicity of over active glutamate, yet Riluzole only prolongs the average ALS patient’s lie by about 2-3 months [3]. Resources are being put into finding alternative treatments with the hope of curing this disease. A supplement that is being looked into for managing ALS is Vitamin D supplementation, which acts as an anti-inflammatory agent counteracting the toxic inflammation response due to over excitation of glutamatergic neurons. It also strengthens muscles being increasing ATP production and Ca2+ uptake [1]. Another treatment being looked into is using stem cells to grow new motor neurons that can then be grafted onto an ALS afflicted patient and using stem cells for therapeutic application [2].

1. Gianforcaro, Alexandro & Hamadeh, Mazen. Vitamin D as a Potential Therapy in Amyotrophic Lateral Sclerosis. CNS Neurosci Ther. (2014); 20(2): 101-11
2. Lunn, Simon et al. Stem Cell Therapies for Amyotrophic Lateral Sclerosis: Recent Advances and Prospects for the Future. Stem Cells. (2014) 10.1002/stem.1628
3. Gordon, Paul. Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management, and Therapeutic Trials. Aging and Disease. (2013); 4(5):295-310

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