Pathophysiology of Parkinson's Disease Flashcards
State 2 causes of Parkinson’s Disease.
Genetic e.g. alpha-synuclein, PINK 1. Environmental substances e.g. toxins - MPTP, e.g. agrochemicals - pesticides.
Where does neuromelanin come from?
Breakdown of dopamine produces neuromelanin.
What gives the substantia nigra a dark colour?
Neuromelanin.
What is the function of caspase 3 in Parkinson’s Disease?
Apoptosis bio-marker.
State 2 things that contribute to neuronal cell death in Parkinson’s Disease.
Oxidative stress in Parkinson’s Disease. Alpha synuclein to the build up of impaired protein handling.
State 2 ways anti-oxidants are produced in Parkinson’s Disease.
Auto-oxidation of dopamine to form neuromelanin. Dopamine metabolism by mono-amine oxidase
What reaction is responsible for production of free radicals which destroy dopamine producing cells?
Fenton reaction (H2O2 oxidised to hydroxide ion).
Parkinson’s Disease also have reduced glutathione levels (GSH). Why is that dangerous?
Glutathione is an anti-oxidant enzyme system.
What results in elevated levels of Fe2+ to drive the Fenton reaction?
Arrival of glia cells.
Name 2 genes that may have mutated in Parkinson’s Disease.
DJ-1. PINK-1. Parkin.
Why are the mutations of genes DJ-1 and PINK-1 dangerous in Parkinson’s Disease?
Results in the clumping of alpha-synuclein which can deposit in lewy bodies.
Explain the direct pathway.
Direct pathway between cortex and striatum freezes globus pallidus. This stops the inhibitory effects of the globus pallidus on the thalamus. Allows thalamus to initiate movement
What neurotransmitter is produced by the global pallidus during the direct pathway?
GABA.
What is the difference between the direct and indirect pathway?
Direct pathway involves in the stopping of global palldius so it can’t produce GABA, so thalamus isn’t inhibitied and can activate cortex. Indirect pathway involves subthalamic nucleus which increases suppression on thalamus. Direct pathway initiates movement. Indirect pathway prevents unwanted movements.
Patients with Parkinson’s Disease have activation of which pathway, direct or indirect pathway?
Indirect.
Why is there less GABA produced by the Global Pallidus during Parkinson’s Disease (INHIBTION of indirect pathway)?
Dopamine is acting on different receptors: D2R– instead of D1R++, in the striatum.
State the two neurotransmitters that work together in the basal ganglia.
Dopamine and Glutamate.
