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21 Cards in this Set
- Front
- Back
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What are some environmental causes of PD?
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6-OH-Dopamine and MPTP
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What are some genetic causes of PD?
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alpha-synuclein (PARK1) overexpression, E3 ligase (PARK2) is lost
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Fill in the blanks: PD is associated with the degeneration of the ________ pathway located in the Substantia ____ within the brain.
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nigrostriatal; nigra
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PD is associated with the loss of which type of dopamine neurons?
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D2
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PD is thought to occur when the balance between ___ and ___ is disrupted.
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Ach and dopamine
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What happens to alpha-synuclein that causes cell death?
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It aggregates.
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MPPP is metabolized to what product that can cross the BBB?
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MPTP
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MPPP is ultimately metabolized to MPP+. What does MPP+ affect in the brain?
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Production of free radicals, which induce neuron membrane damage; semi-quinone and ortho-quinone production
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Dopamine reaction with MAO and oxygen produces what toxic species?
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A toxic aldehyde and hydrogen peroxide.
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Name two types of DA metabolism inhibitors.
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COMT inhibitors and MAO inhibitors.
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MAO inhibitors increase cell survival by activating which two molecules?
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BCL2 and BCL-Lx.
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MAO inhibitors downregulate which two molecules that normally trigger apoptosis?
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BCL-associated death promoter (BAD) and BCL2-associated protein X (BAX).
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What is the cheese reaction?
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Tyramine and fermented foods (like cheese) enter circulation and release noradrenaline to produce high blood pressure.
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What type of inhibitor is associated with the cheese reaction?
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MAOa inhibitor (or an MAOb inhibitor administered at a high enough dose to inhibit MAOa).
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What is L-DOPA administered with and why?
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AADC inhibitors; this prevents L-DOPA from being converted to dopamine outside of the brain.
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What AADC inhibitor did we talk about?
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Carbidopa
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What type of contact does Ser 193 make with D2 agonists?
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H-bonding
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What type of contact does Phe 390 make with D2 agonists?
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pi-pi
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What type of contact does Asp 114 make with D2 agonists?
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Ionic interaction
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What is the energetic value of H-bonds, pi-pi bonds, pi-cation bonds and ionic interactions?
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2-5kcal/mol; 2-3kcal/mol, 3-10kcal/mol
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What molecule that we learned about in the first section (a component of duodote) does carbidopa resemble and why?
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Pralidoxime chloride; alpha effect (hydrazine analog)
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