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Flashcards

MBOD- Parkinson's

George West MBOD ! English 43 cards

Cards in this deck (43)

  1. 1Who discovered Parkinson's and in what year? What did he describe it in?James Parkinson's
    Discovered it in 1817, describing it as involuntary tremulous motion, lessened muscle power in action and even when supported etc
  2. 2Symptoms of Parkinson's?Lack of facial expression
    Lack of arm swing when walking
    Turning around takes more steps
    Hypophonia, deep voice
  3. 3What is Parkinson's? What does it affects?Progressive Neurodegenerative disorder
    Affects 2-4% of population over age of 60
    Movement disorder caused by death of dopaminergic neurons in the substantial Niagra
    Additi nail symptoms are disruption of autonomous functions like heart rate and digestion, and cognitive deficits leading to dementia
  4. 4What is Parkinson's-plus?Additional parts of the brain are affected, leading to additional symptoms
  5. 5Where are the two dopaminergic nuclear ( regions of the brain that project dopamine neurons?Substantia Niagra
    Ventral tegmental area
  6. 6Dead dopamine neurons in the substantia Niagra that lead to motor symptoms show black regions when imaged. Why?Dead dopamine neurons release neuromelanin
  7. 7What is dopamine derived from?Tyrosine
  8. 8What packages dopamine into vesicles?Vesicular monoamine transporters
  9. 9Where are dopamine receptors found?Pre and post synaptically
  10. 10What re-uptake dopamine for reuse and recycle?Dopamine transporters
  11. 11How does L-Dopa effect the dopamine system?It is a drug that can enter BBB
    It is converted to dopamine in the brain
    Dopamine itself cannot enter BBB, so this is a way of increasing conc of dopamine in neuronal cells that are still alive
  12. 12How do antipsychotics affect dopamine system?Block dopamine receptors, so don't have positive effects on Parkinson's, hence why typical schizophrenic drugs can cause Parkinson's like symptoms
  13. 13How do Bupropion, Amphetamine and cocaine affect dopamine system?Inhibit the reputable of dopamine by dopamine transporters
    This keeps high concentrations of dopamine in the synoptic cleft, leading to more AP, and higher EPSP
  14. 14What is Parkinsonism?Other syndromes that results from the death of substantia niagra neurons
  15. 15Two types of Parkinsonism?Juvenile and drug induced
  16. 16What is juvenile Parkinsonism?Recessive genetic disorder caused by mutation in DJ-1
    Two copies of mutated DJ1 can cause Parkinson's in youth
  17. 17MPTP is a neurotoxin that leads to Parkinson's. What's can cause this? How does it do this?Street drugs, spike in 1980s
    MPTP is taken up by dopamine transporters and kills neurons
  18. 18How can mutations in Parkin and Park1 lead to Parkinson's?Involved in degradation of inactive or dead mitochondria from ubiquitin system
    Mutations lead to lack of degradation of these receptors, leading to cellular apoptosis, this death of dopaminergic neurons
  19. 19There are currently no treatments that target the disease mechanisms, but what is Ldopa therapy? Side effects?Drug of L dopa across BBB to increase dopamine
    Tolerance increases as you take more, so need to up dose
    Lead to side affects such as fatigue and dry mouth
  20. 20What is deep brain stimulation therapy? Side effects?It's a surgery option impailing an electrode into brain, and delivers deep electro pulses into brain from a generator
    Overrides current brain activity and gets rid of motor symptoms
    Invasive surgery can lead to haemorrhage and stroke :(
  21. 21What is translation of detail or stem cells therapy for Parkinson's?Replace those cells that have died, but by the time symptoms show, disease is advanced, so 80% of neuron are already dead, so this is only a symptoms treatment
  22. 22What drug is thought to possibly save neurones, but the mechanism is unknown?Aspirin
  23. 23Ideally, what would be the best way to treat and diagnose Parkinson's?Screen patients early and detect PD early, before it becomes highly symptomatic
  24. 24What does sporadic mean?PD is sporadic. Randomally forms and causes change
  25. 25In PD, what are the protein aggregates called? What form this aggregates?Dopamine neurons are full of aggregates called Lewy bodies
    Lewy bodies are made up of alpha-synuclein (a-synuclein)
  26. 26How can restriction enzymes detect mutations?Cut at a particular sequence of DNA, so if genetic sequence is mutated, restriction enzymes cuts will change, thus can identify mutations
  27. 27What gene has been identified to be mutated in familIal PD?A-synuclein gene
    Rare!
  28. 28Difference between mutation and polymorphism?Mutation is away from normal
    Polymorphism is a DNA sequence variation that is common in population
  29. 29What else other than mutations can cause a-synuclein aggregation? What chemical can induce this?Oxidative stress
    It is an imbalance between production of oxygen free radicals and the bodies ability to counteract it with antioxidants
    Rotenone ( given to rats, make Lewy bodies)
  30. 30What are synucleinopathies?Disorders characterised by filamentous a-synuclein that lead to Lewy bodies
  31. 31Dementia can also be formed by Lewy bodies,where in the brain is this?Cortex, forming more complex symptoms
  32. 32What is multiple system atrophy?Oligodendrites in multiple brain regions affected by a-synuclein in myelinated glial cells in the brain
  33. 33What is the gene that encodes a-synuclein protein?SNCA
  34. 345 types of SNCA mutations?1. A35T- leading to early onset of PD
    2. A30P typical PD
    3.E46K dementia with Lewy bodies
    4. SNCA duplication, typical PD, autosomal dominant
    5. SNCA triplication, early onset of Parkinsonism and dementia
  35. 35How can you make preformed fibrils (PFFs)?Small bit of protein in test tube and shake it
  36. 36What happens to production of tyrosine hydroxylase (enzyme that converts tyrosine to L-dopa) during Parkinsonism?After 30 days, still lots of TH but fibres start to aggregate
    After 180, even less TH
  37. 37What does decreasing amount of tyrosine Hydrolase show when staining brain slices?Fibrils are pathogenic and cause development of Lewy bodies as well as death of substantia Niagra
  38. 38Where is a-synuclein found?Presynaptically, is abundant in brain
    Involved in presynaptically activity
  39. 39What does the N-terminal repeat domain encode? How does this primary sequence dictate its functionAn extended alpha helix, it is a series that repeats every 11 residues, presenting an amphiphathic helix
    It resembles lipid binding helixes, found in Apolipoproteins
    Presented in snorkel model (1991 segrest et al)
  40. 40Explain the folding of a-synuclein in different environments..When proteins alone, it is completely unfolded with a random coil structure
    In the presence of lipid, it is an Alpha helix
    In amyloid fibres, it is a beta sheet
    It's large number of stable conformations may explain its vulnerability to mis folding
  41. 41Function of a-synuclein?Presynaptically protein which regulates membrane vesicles trafficking
    Knockout mice display altered dopamine transmission, where by less dopamine was transmitted at synapse
    Effects how vesicles are recycled and taken back into presynapse neuron
  42. 42How does a-synuclein over expression effect structure of synapse?Leads to enlargement of pre synaptic terminals and moulds together membrane structures
  43. 43A-synucleim aggregates in vesicle structures, lysosomes and clogs around the mounded structures.this leads to mis regulation of synaptic vesicle recycling and transmission What forms after this?Lewy bodies!

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! MBOD Flashcards on MBOD- Parkinson's , created by George West on 29/04/2016.
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