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group_1_presentation_1_-_als [2019/02/01 17:16] chens60 [Stem Cells] |
group_1_presentation_1_-_als [2019/02/01 21:26] (current) achunaia [Riluzole] |
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| - | <box 40% width centre|> {{ :alsneurons.png?nolink&400 |}}</box| Figure 1. Neuron.> | + | <box 40% width centre|> {{ :alsneurons.png?nolink&400 |}}</box| Figure 1. Motor Neuron.> |
| ====== What is Amyotrophic Lateral Sclerosis (ALS)? ====== | ====== What is Amyotrophic Lateral Sclerosis (ALS)? ====== | ||
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| ==== Impairment of Axonal Structure or Transport Defects ==== | ==== Impairment of Axonal Structure or Transport Defects ==== | ||
| - | Impairment of axonal transport and structure can be caused by many different pathways triggered by mutant SOD1. Mechanisms such as the lack of mitochondrial function, disruption of kinesin function, energy depletion, and excitotoxicity caused by glutamate, lead to the impairment of axonal transport/structure. Many experiments conducted on mice with mutant SOD1 displayed loss of defects in axonal transport in the early process of the disease. The impairment of the structure leads to build up of mitochondria, autophagosomes, and neurofilaments in the damaged motor neurons, which eventually causes the death of the neurons. | + | Impairment of axonal transport and structure can be caused by many different pathways triggered by mutant SOD1 (Zariei et al., 2015). Mechanisms such as the lack of mitochondrial function, disruption of kinesin function, energy depletion, and excitotoxicity caused by glutamate, lead to the impairment of axonal transport/structure (Zariei et al., 2015). Many experiments conducted on mice with mutant SOD1 displayed loss of defects in axonal transport in the early process of the disease. The impairment of the structure leads to build up of mitochondria, autophagosomes, and neurofilaments in the damaged motor neurons, which eventually causes the death of the neurons (Zariei et al., 2015). |
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| - | <box 40% width centre|> {{ :playground:advancedriluzole.png?400 |}}</box| Figure 6. Role of Riluzole.> | + | <box 40% width centre|> {{ :playground:advancedriluzole.png?400 |}}</box| Figure 6. The mechanism of Riluzole.> |
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| Treatment with a drug called diacetylbis(N(4)-methylthiosemicarbazonato) copper II (CuATSM) has the potential to reduce the symptoms, and slow the advancement of familial ALS. The role of this drug is to penetrate the blood-brain barrier and deliver copper to body cells that are copper deficient (Irving, 2019). According to ALS Therapy Development Institute (2016), this is significant as these cells are able to use copper to prevent the misfolding of proteins that causes ALS (ALS Therapy Development Institute, 2016). According to Xia (n.d.), In humans it is specifically to prevent the misfolding of the SOD1 protein which would affect motor neurons by causing endoplasmic reticulum, proteasome, and mitochondrial stress that influences cell death (Xia, n.d.). Furthermore, mutated SOD1 modifies many cellular pathways and functions including axonal transport, RNA processing, etc. which leads to muscle atrophy (Xia, n.d.). Carvalho (2019), concluded that CuATSM improves lung and cognitive function during Phase 1 human clinical trials (Carvalho, 2019). This was measured using the forced vital capacity and Edinburgh cognitive and behavioural ALS Screen (ECAS) scoring system (Carvalho, 2019). Patients with lower doses of CuATSM experienced minor improvements in these scores over 24 weeks compared to those with higher doses (Carvalho, 2019). Phase 2 clinical trials will be held in 2019 to confirm its impact on biological activities using larger and randomized sample sizes, implementing placebo controls, and using a double-blind experiment (Irving, 2019). | Treatment with a drug called diacetylbis(N(4)-methylthiosemicarbazonato) copper II (CuATSM) has the potential to reduce the symptoms, and slow the advancement of familial ALS. The role of this drug is to penetrate the blood-brain barrier and deliver copper to body cells that are copper deficient (Irving, 2019). According to ALS Therapy Development Institute (2016), this is significant as these cells are able to use copper to prevent the misfolding of proteins that causes ALS (ALS Therapy Development Institute, 2016). According to Xia (n.d.), In humans it is specifically to prevent the misfolding of the SOD1 protein which would affect motor neurons by causing endoplasmic reticulum, proteasome, and mitochondrial stress that influences cell death (Xia, n.d.). Furthermore, mutated SOD1 modifies many cellular pathways and functions including axonal transport, RNA processing, etc. which leads to muscle atrophy (Xia, n.d.). Carvalho (2019), concluded that CuATSM improves lung and cognitive function during Phase 1 human clinical trials (Carvalho, 2019). This was measured using the forced vital capacity and Edinburgh cognitive and behavioural ALS Screen (ECAS) scoring system (Carvalho, 2019). Patients with lower doses of CuATSM experienced minor improvements in these scores over 24 weeks compared to those with higher doses (Carvalho, 2019). Phase 2 clinical trials will be held in 2019 to confirm its impact on biological activities using larger and randomized sample sizes, implementing placebo controls, and using a double-blind experiment (Irving, 2019). | ||
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| + | <box 30% width centre|> {{ :cuatsm.png?300 |}}</box| Figure 8. Structure of CuATSM.> | ||
| ====== ALS PowerPoint ====== | ====== ALS PowerPoint ====== | ||
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| Bogdanov, M., Brown Jr, R. H., Matson, W., Smart, R., Hayden, D., O’Donnell, H., ... & Cudkowicz, M. (2000). Increased oxidative damage to DNA in ALS patients. Free Radical Biology and Medicine, 29(7), 652-658. | Bogdanov, M., Brown Jr, R. H., Matson, W., Smart, R., Hayden, D., O’Donnell, H., ... & Cudkowicz, M. (2000). Increased oxidative damage to DNA in ALS patients. Free Radical Biology and Medicine, 29(7), 652-658. | ||
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| + | Bryson, H. M., Fulton, B., & Benfield, P. (1996). Riluzole. Drugs, 52(4), 549–563. https://doi.org/10.2165/00003495-199652040-00010 | ||
| Brooks, B. R., Miller, R. G., Swash, M., & Munsat, T. L. (2000). El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis and other motor neuron disorders, 1(5), 293-299. | Brooks, B. R., Miller, R. G., Swash, M., & Munsat, T. L. (2000). El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis and other motor neuron disorders, 1(5), 293-299. | ||
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| Learning, L. (n.d.). Biology for Majors I. Retrieved from https://courses.lumenlearning.com/wm-biology1/chapter/reading- electron-transport-chain/ | Learning, L. (n.d.). Biology for Majors I. Retrieved from https://courses.lumenlearning.com/wm-biology1/chapter/reading- electron-transport-chain/ | ||
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| + | Lewerenz, J., & Maher, P. (2015). Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence? Frontiers in Neuroscience, 9. https://doi.org/10.3389/fnins.2015.00469 | ||
| Mitsumoto, H. (1997). Diagnosis and progression of ALS. Neurology, 48(4 Suppl 4), 2S-8S. | Mitsumoto, H. (1997). Diagnosis and progression of ALS. Neurology, 48(4 Suppl 4), 2S-8S. | ||
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| Riluzole Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD. (n.d.). Retrieved from | Riluzole Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD. (n.d.). Retrieved from | ||
| https://www.webmd.com/drugs/2/drug-12138/riluzole-oral/details | https://www.webmd.com/drugs/2/drug-12138/riluzole-oral/details | ||
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| + | Rothstein, J. D. (1996). Therapeutic horizons for amyotrophic lateral sclerosis. Current Opinion in Neurobiology, 6(5), 679–687. https://doi.org/10.1016/S0959-4388(96)80103-6 | ||
| Seals, R. M., Hansen, J., Gredal, O., & Weisskopf, M. G. (2016). Physical Trauma and Amyotrophic Lateral Sclerosis: A Population-Based Study Using Danish National Registries. //American Journal of Epidemiology,183//(4), 294-301. doi:10.1093/aje/kwv169 | Seals, R. M., Hansen, J., Gredal, O., & Weisskopf, M. G. (2016). Physical Trauma and Amyotrophic Lateral Sclerosis: A Population-Based Study Using Danish National Registries. //American Journal of Epidemiology,183//(4), 294-301. doi:10.1093/aje/kwv169 | ||
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| Swash, M. (2018). Physical activity as a risk factor in ALS. //Journal of Neurology, Neurosurgery & Psychiatry,89//(8), 793-793. doi:10.1136/jnnp-2018-318147 | Swash, M. (2018). Physical activity as a risk factor in ALS. //Journal of Neurology, Neurosurgery & Psychiatry,89//(8), 793-793. doi:10.1136/jnnp-2018-318147 | ||
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| + | Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., … Dingledine, R. (2010). Glutamate Receptor Ion Channels: Structure, Regulation, and Function. Pharmacological Reviews, 62(3), 405–496. https://doi.org/10.1124/pr.109.002451 | ||
| What is ALS? - ALS Society of Canada. (n.d.). Retrieved from https://www.als.ca/about-als/what-is-als/ | What is ALS? - ALS Society of Canada. (n.d.). Retrieved from https://www.als.ca/about-als/what-is-als/ | ||
