Parkinson's Disease Flashcards
Which protein(s) Is/are suspected in PD
alpha- Synuclein
Parkin
What region of the brain is affected by pd
basal ganglia
Pd environmental risk factors
Neurotoxin exposure
Developmental exposure to pesticides
TBI
Iatrogenic
protective factor in pd
tobacco smoking
pd pathophys
1) depigmentation of pars compacta in substantia nigra –> DA neuron loss
2) Alpha synuclein dysregulation –> formation of cortical and nigral Lewy Bodies
How much nigral DA must be lost for PD?
70-80%
Looking at PET scanns what is most notibly lost?
VMAT2. Also DAT
Why aren’t rats affected by MPTP like humans? No los of nigral neurons?
Rats have MAO-B in the BBB, MPP+ formed and does not cross the BBB
Substantial loss of DA before Diagnosis. What are possible predictors?
Hyposmia,
changes in smell perception,
Constipation,
REM-Sleep behavior
PD symptoms
Resting Tremor Festinating Gait Bradykinesia Reduced arm swinging Mask Freezing at movement initiation
What causes the resting tremor?
Loss of ACh in basal ganglia
Autonomic symptoms of PD
Fatigue,
olfactory disturbances
Hyperalgesia
Sexual dysfunction
Cognitive impairment
Cognitive: -Late onset -Frontal corex and subcortical regions -Lack of initiative, slowness, forgetfulness, Psychiatric: -Depression, Anxiety
What type of drugs might cause cognitive impairment
BBB crossing muscarinic antagonistsI
Stalevo
L-dopa, carbidopa, entacapone
When to use MAO-AIs vs MAO-BIs
MAO-A for depression and PD, Increases DA, NE, 5HT
MAO-B increases DA only
Problems with L-dopa therapy
- Catabolism increases Free radicals
- ADRs: hallucinations, insomnia, nausea
- Peripheral catabolism
What enzyme is involved in normal metabolism of DA produced H2O2
Glutathione peroxidase
Trend: Levodopa response over time
Time spent in symptomatic control decreases over time: Narrower peaks in advanced PD
Non-pharmaco
Deep brain stimulation in subthalamic nucleus
What does stimulating the subthalamic nucleus do?
Mimics the intrinsic pathway
GDNF
Glia derived neurotrophic factor
Why doesn’t injecting GDNF into SN work
No GDNF receoptors
How to administer GDNF, what happens?
Injected into striatum, brought up the axon via retrograde transport back to nucleus located in SN
GDNF MOA?
Transcription Factor
