Parkinson's Disease

Question 1

Which protein(s) Is/are suspected in PD

Answer 1

alpha- Synuclein

Parkin

Question 2

What region of the brain is affected by pd

Answer 2

basal ganglia

Question 3

Pd environmental risk factors

Answer 3

Neurotoxin exposure
Developmental exposure to pesticides
TBI
Iatrogenic

Question 4

protective factor in pd

Answer 4

tobacco smoking

Question 5

pd pathophys

Answer 5

1) depigmentation of pars compacta in substantia nigra –> DA neuron loss
2) Alpha synuclein dysregulation –> formation of cortical and nigral Lewy Bodies

Question 6

How much nigral DA must be lost for PD?

Answer 6

70-80%

Question 7

Looking at PET scanns what is most notibly lost?

Answer 7

VMAT2. Also DAT

Question 8

Why aren’t rats affected by MPTP like humans? No los of nigral neurons?

Answer 8

Rats have MAO-B in the BBB, MPP+ formed and does not cross the BBB

Question 9

Substantial loss of DA before Diagnosis. What are possible predictors?

Answer 9

Hyposmia,
changes in smell perception,
Constipation,
REM-Sleep behavior

Question 10

PD symptoms

Answer 10

Resting Tremor
Festinating Gait
Bradykinesia
Reduced arm swinging
Mask
Freezing at movement initiation

Question 11

What causes the resting tremor?

Answer 11

Loss of ACh in basal ganglia

Question 12

Autonomic symptoms of PD

Answer 12

Fatigue,
olfactory disturbances
Hyperalgesia
Sexual dysfunction

Question 13

Cognitive impairment

Answer 13

Cognitive: 
-Late onset
-Frontal corex and subcortical regions
-Lack of initiative, slowness, forgetfulness, 
Psychiatric:
-Depression, Anxiety

Question 14

What type of drugs might cause cognitive impairment

Answer 14

BBB crossing muscarinic antagonistsI

Question 15

Stalevo

Answer 15

L-dopa, carbidopa, entacapone

Question 16

When to use MAO-AIs vs MAO-BIs

Answer 16

MAO-A for depression and PD, Increases DA, NE, 5HT

MAO-B increases DA only

Question 17

Problems with L-dopa therapy

Answer 17

• Catabolism increases Free radicals
• ADRs: hallucinations, insomnia, nausea
• Peripheral catabolism

Question 18

What enzyme is involved in normal metabolism of DA produced H2O2

Answer 18

Glutathione peroxidase

Question 19

Trend: Levodopa response over time

Answer 19

Time spent in symptomatic control decreases over time: Narrower peaks in advanced PD

Question 20

Non-pharmaco

Answer 20

Deep brain stimulation in subthalamic nucleus

Question 21

What does stimulating the subthalamic nucleus do?

Answer 21

Mimics the intrinsic pathway

Question 22

GDNF

Answer 22

Glia derived neurotrophic factor

Question 23

Why doesn’t injecting GDNF into SN work

Answer 23

No GDNF receoptors

Question 24

How to administer GDNF, what happens?

Answer 24

Injected into striatum, brought up the axon via retrograde transport back to nucleus located in SN

Question 25

GDNF MOA?

Answer 25

Transcription Factor