Unformatted text preview: Parkinson's Model in Drosophila
By Chris Bostick BioNB420 What is Parkinson's Disease Parkinson's disease is a movement disorder that is chronic and progressive, meaning that symptoms continue and worsen over time. As many as one million Americans suffer from Parkinson's disease http://www.pdf.org/AboutPD/index.cfm Who Gets it Usually symptoms appear after the age of 50 and the risk of getting Parkinson's increases with age Statistically, men are more prone to getting Parkinson's then women. http://www.parkinsons.org.uk/HomePage.asp?NodeID=89586 Causes The Specific causes are unknown Occurs when dopamine producing cells in basal Ganglia die. Dopamine is a chemical messenger that helps regulate movement. http://www.pdf.org/AboutPD/index.cfm http://www.parkinsons.org.uk/Templates/Internal.asp?NodeID=91835 http://www.familydoctor.co.uk/htdocs/PARKINSONS/PARKINSONS_specimen.html Causes Cont. Some believe that build up of a protein called Alpha synuclein maybe related to Parkinson's The protein may abnormally clump up, form the clogging deposits and eventually choke the dopamine cells to death. Parkin is a amino acid protein involved in the ubiquitinproteasome system that might be involved with AlphaSynuclein. http://apu.sfn.org/content/Publications/BrainBriefings/parkinson.html#fullsize http://www.webbooks.com/MoBio/Free/Ch10HParkinson.htm How Parkin Works www.emdbiosciences.com/html/CBC/parkinson.htm Lewy Bodies and Neurites aSynuclein, Parkin and synphilin1 represent the major components of Lewy bodies. Small, dense deposits, termed Lewy bodies or Lewy neurites, stud the brains of patients with Parkinson's disease. http://apu.sfn.org/content/Publications/B Other Causes Gene Inheritance: 15 to 25 percent of people with Parkinson's report having a relative with the disease. researchers have found that people with an affected firstdegree relative have a twotothree fold increased risk of developing Parkinson's. Environmental Factors: such as physical trauma, exposure to chemicals and infections, and nutrition. Synthetic narcotic agent called MPTP can cause immediate and permanent parkinsonism if injected. http://www.pdf.org/AboutPD/causes.cfm http://www.alzforum.org/res/for/journal/parkin/default.asp Symptoms Tremor: "Resting Tremor" because muscles move when relaxed. Usually tremor starts on one side of the body and moves to the other as disease progresses. Rigidity: Stiffness or inflexibility of the muscles. Results in decreased range of motion. Bradykinesia: Person experiencing slow movements. A person with bradykinesia will probably also have incomplete movement, difficulty initiating movements and sudden stopping of ongoing movement. Postural instability or impaired balance and coordination: Instability while standing or impaired balance. http://www.pdf.org/AboutPD/symptoms.cfm Secondary Symptoms Constipation Difficulty swallowing (dysphagia)--saliva and food that collects in the mouth or back of the throat may cause choking, coughing, or drooling Excessive salivation (hypersalivation) Excessive sweating (hyperhidrosis) Loss of bladder and/or bowel control (incontinence) Loss of intellectual capacity (dementia)--late in the disease Psychosocial: anxiety, depression, isolation Scaling, dry skin on the face and scalp (seborrhea) Slow response to questions (bradyphrenia) Small, cramped handwriting (micrographia) Soft, whispery voice (hypophonia) http://www.neurologychannel.com/parkinsonsdisease/symptoms.shtml Diagnosis of Parkinson's No specific test Diagnosis is based on symptoms and ruling out other disorders that produce similar symptoms. A patient must have two or more of the primary symptoms, one of which is a resting tremor or bradykinesia. www.phoenix5.org/glossary/diagnosis Treatment No Cure Medication to relieve symptoms. Examples: Levodopa Dopamine Agonists http://www.neurologychannel.com/parkinsonsdisease/treatment.shtml Treatment Cont. Surgery: Deep Brain Stimulation(DBS) By using deep brain electrodes normal cycle of electrical signals is maintained. DBS can be applied to the thalamus, the globus pallidus and the subthalamic nucleus. http://www.pdf.org/AboutPD/index.cfm Parkinson's in Drosophila Transgenic flies expressing either the normal or mutant forms of human asynuclein were generated by M.B. Feany and W.W. Bender. Wildtype human alpha synuclein and two mutant forms of human a synuclein in nerve cells were created. The Transgenic flies exhibited traits of Parkinson's Disease. http://www.nature.com/nature/journal/v404/n6776/full/404394a0.html#B8 Traits Exhibited Agedependent loss of dopaminergic neurons. Presence of Lewy bodylike inclusions composed of asynuclein Loss is restricted to the dopaminergic neurons within the nervous system. filaments. Loss of motor function. Loss of dopaminergic neurons occurs at an advanced age Loss is restricted to the nervous system http://www.molbio.princeton.edu/courses/mb427/2001/projects/03/neuro.htm A comparison Model http://www.sciencemag.org/cgi/content/full/288/5466/631 Interesting Discovery A Drosophila homolog of human PARK2 and characterized its parkin null flies have 30% lower mass than wildtype controls which is in part accounted for by a reduced cell size and number. loss of parkin results in progressive degeneration of most indirect flight muscle (IFM) expression and null phenotype. http://dev.biologists.org/cgi/content/abstract/131/9/2183 Work Cited http://www.pdf.org/AboutPD/index.cfm http://www.parkinsons.org.uk/HomePage.asp?NodeID=89586&int1stParentNodeID=8 http://www.neurologychannel.com/parkinsonsdisease/ http://www.alzforum.org/res/for/journal/parkin/default.asp http://apu.sfn.org/content/Publications/BrainBriefings/parkinson.html http://www.webbooks.com/MoBio/Free/Ch10HParkinson.htm http://repository.upenn.edu/dissertations/AAI3087369/ http://www.sciencemag.org/cgi/content/full/288/5466/631 http://www.nature.com/nature/journal/v404/n6776/full/404394a0.html#B8 http://www.molbio.princeton.edu/courses/mb427/2001/projects/03/neuro.html http://www.emdbiosciences.com/html/CBC/parkinson.htm http://dev.biologists.org/cgi/content/abstract/131/9/2183 A Drosophila model of Parkinson's disease Mel B. Feany1 and Welcome W. Bender 404, 394398 (23 March 2000) ...
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- Fall '05