1. THE IDEA: The lack of neuroprotective therapies and limited treatment strategies intensify the urgency for the development of novel approaches to treat Parkinson’s disease (PD). Here we propose fast axonal transport (FAT) as a novel target for therapeutics development for PD. The underlying logic behind this proposal is two fold. First, several studies have reported defects in axonal transport in PD and suggested its possible contribution to the degeneration of neuronal processes in PD. Second, our laboratory has made several key contributions to FAT and neural plasticity and memory storage. Hence we are in an ideal position to study the function of key mediators of FAT in PD in order to identify novel targets for therapeutics development. …show more content…
FAT and PD: Kinesin heavy chain (KHC), kinesin light chain (KLC) and microtubules (MTs) are the three main components of FAT to synapses from the cell body. KHC and KLC mediate transport of cargos such as proteins, RNAs, and organelles, such as mitochondria, along MTs to synapses. Here we discuss several studies that suggest an important role for FAT in PD pathogenesis. A recent study using immunohistochemistry suggests a significant decrease in the level of KHC and KLC1 in nigral neurons in sporadic PD cases as well as in the rat genetic PD model (overexpression of human mutant α-synuclein (A30P)), which lead to other nigral cell-related pathology (Chu et al., 2012). This reduction was significantly greater in nigral neurons containing α-synuclein inclusions. Furthermore, the viral overexpression of A53T α-synuclein has been demonstrated to reduce the expression of kinesins Kif1A, Kif1B, Kif2A and Kif3A in the striatum (Chung et al., 2009). PD-associated α-synuclein mutants (A30P or A53T) have also been found to precede reduced axonal transport of α-synuclein, which contributes to the perikaryal accumulation of α-synuclein, Lewy body formation and neuritic abnormalities in diseased brain (Saha et al., 2004). α-synuclein also affects the phosphorylation status of molecular motors and thereby negatively regulating the transport. The failure of axonal transport may lead to further protein depositions of α-synuclein and tau within the cell body (Lei et al., 2010).
Emery-Dreifuss muscular dystrophy is a rare form of muscular dystrophy characterized by early onset contractures of the elbows, achilles tendons and post-cervical muscles with progressive muscle wasting and weakness It is also associated with heart complications like cardiomyopathy and arrhythmia which in both cases can lead to death. Cardiomyopathy is a heart disease which affects the muscles of the heart. In cardiomyopathy is muscles get rigid, enlarged or thick. They also sometimes changed by scar tissues. On the other hand arrhythmia is a disorder with the rhythm or rate of heartbeat. The heart can beat fast, which is called tachycardia or it could be beating too slow, which is called bradycardia. Emery-Dreifuss muscular dystrophy is characterized by early onset of contractures and humeroperoneal distribution. Humeroperoneal refers to effects on the humerus and fibula. The genes known to be responsible for EDMD encode proteins associated with the nuclear envelope: the emerin and the lamins A and C.
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).
Varanese, S., Birnbaum, Z., Rossi, R., & Di Rocco, A. (2010). Treatment of Advanced Parkinson's Disease. Parkinson's Disease.
Duane Syndrome is an inherited unusual type of strabismus (squint) most often described by the incapability of the eye(s) to move inwards, outwards individually or together. This was first reported via ophthalmologists Jakob Stilling in 1887 and also Siegmund Türk in 1896. The syndrome was named after Alexander Duane, who explained the disorder more specifically in 1905. The syndrome is described as a miswiring of the eye muscles, causing eye muscles to tighten when they don’t need to and other eye muscles not to tighten when they need to. Very often patients get the syndrome by the age of 10 and it is more common in females (60% of the cases) than males (40% of the cases). Although the eye is usually the abnormality associated with Duane Syndrome, there are other bodily functions that can be affected. Duane syndrome cannot be cured, because the cranial nerve is missing and it cannot be replaced. The gene known as “SALL4” has been associated as a cause of this condition.
Goldmann, David R., and David A. Horowitz. American College of Physicians Home Medical Guide to Parkinson's Disease. New York: Dorling Kindersley Pub., 2000. Print.
With more than 200,000 US cases per year, Parkinson’s disease has become a major part
1. James suffers from a condition called Duchenne muscular dystrophy. Explain the full meaning of this name.
The path physiology of Parkinson’s disease is the pathogenesis if Parkinson disease is unknown. Epidemiologic data suggest genetic, viral, and environmental toxins as possible causes. Nigral and basal loss of neurons with depletion of dopamine, an inhibitory neurotransmitter, is the principal biochemical alteration in Parkinson disease. Symptoms in basal ganglia disorders result from an imbalance of dopaminergic (inhibitory) and cholinergic (excitatory) activity in the caudate and putamen of the basal ganglia.
Umemoto, G., Tsuboi, Y., Kitashima, A., Furuya, H., & Kikuta, T. (2010). Impaired food transportation in parkinson's disease related to lingual bradykinesia. Dysphagia, (26), 250-255.
It is estimated that 1 out of every 5,600-7,700 boys ages 5-24 have Duchene or Becker muscular dystrophy. (“Data & Statistics,” 2012 April 6) Muscular dystrophy is a group of genetic diseases defined by muscle fibers that are unusually susceptible to damage. There are several different types of muscular dystrophy some of which shorten the affected person’s lifespan. (“Muscular dystrophy: Types and Causes of each form,” n.d.) There is a long history of the disorder but until recently there wasn’t much knowledge of the cause. (“Muscular Dystrophy: Hope through Research,” 16 April 2014) Symptoms are obvious and can be seen as soon as a child starts walking. (“Muscular Dystrophy,” 2012 January 19) Although muscular dystrophy mostly affects boys, girls can get it too. (“Muscular Dystrophy,” 2012 January 19) There is no cure for muscular dystrophy but there are several types of therapy and most types of muscular dystrophy are still fatal. (“Muscular Dystrophy: Hope through Research,” 16 April 2014)
Parkinson’s disease is a chronic, progressive neurodegenerative disorder characterised by resting tremor, slowed movements, rigidity and postural instability (Casey G, 2013). It is the second most common neurodegenerative disorder after Alzheimer’s (Martin and Mills, 2012). There is a great variability in reported incidence rates, probably due to difference in diagnostic criteria and case ascertainment, with reported rates in Australia and in Western countries ranging from 8.6 to 19.0 per 100,000 population (J Macphee and D Stewart, 2012). The two main brain structures affected by Parkinson’s are the substantia nigra pars compacta, which is located in the midbrain and other parts of the basal ganglia, w...
Most signs and symptoms of Parkinson disease correspond to one of three motor deficiencies: bradykinesia, akinesia, tremor, and rigidity. The first two qualities are usually present before tremor, but often attributed to aging by the patient and even the physician, and thus the disease is rarely diagnosed until tremor becomes evident much later. An average of 80% of the nigrostriatal neurons may have already degenerated by the time Parkinsonism is diagnosed, which complicates treatment (Fitzgerald, 130). Bra...
Prion Disease is a lethal thing that does not have a cure. Many people are dying from this and researchers are nowhere near close to finding anything to stop the disease. By making more people aware of this, it can make some that are interested in medicine and science have an drive to help find a cure. Prion Disease is a complex thing to understand completely, especially when there is no prior knowledge about this topic. So explaining the different types and other general information about the disease is important. Some more topics to discuss are cures and symptoms. Some aren’t aware that they have Prion Disease, which can lead to it spreading, and the fact that there isn’t a cure is another problem. Since Prion Disease isn’t a common topic that many hear about daily or even know about. By talking about basic information about Prion Disease and how there isn’t a cure and the symptoms that come with it, people can start to understand how important this really is because many people are dying and by informing society finding a cure with fresh eyes could be done a lot sooner.
Duchenne Muscular Dystrophy, also known as DMD, is the most common form of muscular dystrophy. Muscular dystrophy is a condition that is inherited, and it is when muscles slowly become more and more weak and wasted. Duchenne muscular dystrophy is a form of muscular dystrophy that is very rapid and is most commonly found in boys. In muscle, there is a protein named dystrophin. Dystrophin is encoded by the DMD gene. When boys have Duchenne muscular dystrophy, they do not produce enough dystrophin in their muscles. This causes weakness in their muscles. Parents can tell if their child has duchenne muscular dystrophy by looking for various symptoms.
According to Aberth, "disease is a constant force in human history that has had much more than just demographic repercussions"(Aberth 2007, Pg.X). It has created fear, awareness, pain and frustration for the lack of knowledge of it cause. In 1500 through the 20th century, the primary reasons for disease to spread so effectively are animals, trade routes and colonization/ imperialism. The disease was widely spread through warm climate and the geographic of the world because the virus host bacteria was able to grow and attack the human body.