22 parkinsons Flashcards
when was parkinsons described?
in 1817
-‘shaking palsy’= paralysis with tremor (involuntary muscle contraction)
-disorder of motor functions
what are parkinsons disease features?
progressive neurological disorder
-physical disorders: loss of motor control (tremor, rigidity, bradykinesia (brady=slow+kinesis=movement))
-cognitive disorders: dementia, depression, sleep disorders
what are the parkinsons disease statistics?
-prevalence is 1-2 per 1,000 (0.1-0.2%)
age related
-rare<50 years old
-> 50 yrs old incidence increases by 5-10 folds
what is the biology of what goes wrong in parkinsons?
-parkisons patients have high levels of damaged dopamine producing neurons in the substantia nigra
-they cannot produce dopamine
what is the basal ganglia, substantia nigra, neurons and neurotransmitters?
-basal ganglia: brain region that controls motor functions
-substantia nigra: region that has neurons that produces the neurotransmitter dopamine
-neurons: specialized nerve cells that communicate by electrical or chemical signals
-neurotransmitter: chemical signaling messengers
what is dopamine?
-a neurotransmitter (chemical signaling molecules the brain use to communicate functions)
-in different parts of the brain, dopamine can either regulate motor movement, mood and behavior
-loss of dopamine in the basal ganglia leads to loss of motor functions
what is the mechanism of dopamine?
-dopamine is transmitted from pre-synaptic neuron to post-synaptic neuron to control movement
-in parkinsons pre synaptic neuron do not produce dopamine
-result: post-synaptic neurons do not receive dopamine signal to control muscle movement
what is the problem of creating parkinsons treatment?
damage neurons cannot be repaired
-terminally differentiated; once neurons degenerate, it cannot be reversed
-currently, there are no cures for parkinsons, only management treatments
-pharmaceutical treatments (most common method)
-deep brain simulation (surgical method)
what are the examples of therapeutical treatments?
L-DOPA (L-3,4-dihydrosyphenylalanine)
-precursor to neurotransmitter dopamine
-acts to restore dopamine balance
-invented in 1950s, still the gold standard used in almost all patients
ropinirole
-dopamine agonist (mimic its effect)
-alternative way to activate dopamine receptors
what is the goal of pharmaceutical treatments?
restore dopamine balance inside the brain
1. drugs that increase dopamine (L-DOPA)
2. drugs that mimic dopamine (ropinirole)
3. drugs that inhibit dopamine breakdown (ex: rasagiline)
what is deep brain simulation treatment?
surgical options when medication is not working
-electrodes are connected to regions inside the basal ganglia
-electrical impulse stimulates neural signaling
-works, but unclear exactly how. Thought to trigger the release of electrical, chemical signals to promote neuronal activity
what causes parkinsons?
-the exact cause is unknown
-early diagnosis is difficult, based on motor symptoms
-symptom onset when 50-80% of dopamine neuron is already degenerated
what are the known factors associated with parkinsons?
-age
-head injuries
-genetics
-environmental factors
what are the genetic links to parkinsons?
-gene mutations linked to a small percentage of parkinsons (3-5%), more common in early onset (<50 years old)
-random gene mutations (ex: SNCA, LKRR2, Parkin) that interfere with the maintenance and up-keeping of dopamine neurons
-heritability of disease is extremely low <10% report family history
-can be identified through genetic testing
what are the environmental links to parkinsons?
-majority of research suggest that environmental factors play a very important role in parkinsons development
what does MPP+ do?
inside the neurons, MPP+ blocks the mitochondria leading to death of dopamine receptors
contributions to science:
-drugs that can mimic parkinsons inside the lab
-clues on toxicity of chemicals with similar structures
what is rotenone?
organic origin, naturally produced by plants (derris elliptica)
history of use:
-parasitic mites on animals
-beetles and insects on fruits and veggies
-unwanted fish species in bodies of water
what is rotenones mode of action?
has similar toxic mode of action as MPP+
-target the mitochondria to induce neuron degeneration
-rapidly degraded, toxicity lost after 5-6 days
-generally banned in USA and Canada, but still used as piscicide
what is paraquat?
-one of the most widely used pesticides in the world
-60 years old, >100 crop types
-structural analog of MPP+
-banned in europe unions, controlled use in canada and usa
history of use:
-general herbicide
-aquatic weeds
-seed crops and orchards
what is the mode of action of paraquat?
-highly toxic to humans, especially acute exposure
-persistent in soil, half-life from 16 months to 13 years
-structural similarity to MPP+ allows it to be transported into the neuron by dopamine transporter
-inside the neuron, paraquat damages the mitochondria, which cause damages leading to cell death
what are the problems of heavy metals?
most heavy metals have long half-life
-bioaccumulate at trace levels, chronic exposure lead to cell damage and death
multiple modes of toxicity
-displace essential metals
-damage mitochondria (dopaminergic neuronal death)
what is acrylamide research?
