Parkinson's Disease Flashcards
Symptoms
- Tremor–involuntary movement, usually hands, only one hand or the other
- Rigidity–locked in a certain position
- Slowness of movement
- Postural instability–bad balance
Parkinson’s disease
2nd most common neurodegenerative disease
1.5 million Americans living with PD–85% over age 65
Men at 2X greater risk
Genetic and environmental factors
Executive dysfunction
Problems planning, abstract thinking, failure to inhibit inappropriate behavior
Dementia (late)
Impulse control (due to treatment)
Parkinson’s brain
Substantia nigra–midbrain (reward, addiction, and movement)
Main source of dopamine neurons
Dopamine
1950–Carlsson determined that dopamine functions as a neurotransmitter
Bunny–drug to decrease dopamine->tremor and loss of movement; sad bunny + L-Dopa leads to no tremor and movement
Lewy bodies
1912–Frederic Lewy observes dark stains in specific regions of Parkinson’s patients
Lewy body dementia
Lewy bodies in other parts of the brain resulting in decline of cognitive function
Various cognitive defects, visual hallucinations, REM sleep disruption
Typical degenerates into Parkinson’s
Identifying Lewy body proteins
1995–Alice lazzarini identifies gene responsible for Parkinson’s
PARK 1
PARK 1
Gene responsible for Parkinson's Protein--alpha-synuclein Abundant in brain cells Accumulates at pre-synaptic terminals Function unknown--May aid in dopamine vesicle accumulation
Alpha synuclein
Not very big (140 amino acids)
Intrinsically disordered protein–a protein that lacks any stable secondary or tertiary structure
Autoproteolytic activity–cut its own peptide bonds
Shape determined by where it is in the cell
Parkin
Parkin mutations don’t form Lewy bodies but neurons still die
Are the large protein aggregates (Lewy bodies) a protective measure of the cell?
Treatments for Parkinson’s
L-Dopa–dopamine precursor
Crosses blood brain barrier (dopamine does not)
Natural compound made from tyrosine (tyrosine–>L-Dopa–>dopamine)
Side effects of L-Dopa
Loss of sleep
Vivid dreams
Anxiety/depression (decreased serotonin levels)
Dopamine dysregukation syndrome (addiction)
L-Dopa tolerance
Many patients adapt to increased levels of L-Dopa
Doesn’t convert to dopamine–med won’t work
Treatments for Parkinson’s
- Monoamine oxidase B (MAO B) inhibitors
2. Deep brain stimulation
Monoamine oxidase B (MAO B) inhibitors
Treatment for Parkinson’s
MAOs are enzymes that break down neurotransmitters
MAO A–break down serotonin
MAO B–break down dopamine
Compounds that inhibit these enzymes lead to increase in neurotransmitter
Deep brain stimulation
Treatment for Parkinson’s
Pacemaker for the brain
Stimulate basal ganglia
Complicated and risky surgery
Patients that respond well to L-Dopa are good candidates–however, usually in their 70s so doctors don’t want to operate
If successful, it is very effective–walking, loss of tremor
10-15% death rate due to infection
Potential cures of Parkinson’s
- Glial cell derived neurotrophic factor (GDNF)
2. Conserved dopamine neurotrophic factor (CDNF)
Glial cell derived neurotrophic factor (GDNF)
2002
Growth factor for glial cells
Prevents breakdown of dopaminergic neurons and restores activity to substantia nigra
Needs to be injected directly into the ventricle via surgically implanted pump
Conserved dopamine neurotrophic factor (CDNF)
2008
Shown experimentally more effective (in mice and rats)
Dopamine growth?
Parkinson’s case study
1982–San Francisco
7 patients show up in ER: can’t move properly, stiff limbs, tremors, difficulty speaking
Heroin–>short supply
MPTP synthesized (Super Demerol) with impurities comotose within 3 days
Inject MPTP into rats–nothing
Inject MPTP into primates–same symptoms
Loss of dopaminergic neurons leads to cellular death
