Parks: Degenerative Diseases

Question 1

What proteins are deposited in Alzheimer disease to form inclusions?

Answer 1

Abeta

Tau

Question 2

What happens to proteins when they get old or become misfolded?

Answer 2

they become ubiquinated in the proteasome or they are killed by lysosomes (autophagy)

Question 3

How do inclusions bodies form?

Answer 3

they form when proteins become unfolded but are resistant to degradation –> they form oligomers and begin to aggregate to form large inclusion bodies

**not getting properly degraded by the proteasome or lysosomes

Question 4

What are the cellular consequences of protein aggregation and inclusions?

Answer 4

1. they elicit a stress reaction from the cell
2. directly toxic to the neurons
3. some aggregates behave like prions and spread from neuron to neuron

Question 5

When cells are under stress, what happens?

Answer 5

neurodegeneration –> neuron death

Question 6

When amyloid proteins become misfolded, they form (blank)

Answer 6

Beta-sheet structures called fibrils

Question 7

T/F: Amyloidosis can occur in the brain and the heart

Answer 7

True

Question 8

Two characteristic features of Alzheimer disease

Answer 8

neurofibrillary tangles w/i neuron (leads to plump unhealthy neurons)
amyloid plaques in the interstitial space

Question 9

Where does Alzheimer’s disease usu begin?

Answer 9

hippocampus (around the temporal lobe)

Question 10

Where does A-Beta come from?

Answer 10

it is cleaved by secretases from amyloid precursor protein to form a bunch of different forms of Abeta monomers; the monomers form oligomers which aggregate

Question 11

Amyloid precursor protein is cleaved by secretases to form (blank), which form (blank) that aggregate into plaques and tangles and lead to neuronal damage

Answer 11

Abeta monomers; oligomers

Question 12

What is tau? How is it involved in Alzheimer’s disease?

Answer 12

a microtubular protein which gets hyper-phosphorylated by a kinase that is turned on by Abeta; this causes it to fall off the microtubules, so they are no longer stable

**microtubules are involved in intracellular trafficking

Question 13

Tau is a microtubular protein. It gets (blank) by amyloid-Beta, and falls off of the microtubule. It forms (blank) and leads to (blank) microtubules

Answer 13

phosphorylated; neurofibrillary tangles; destabilized

Question 14

Describe the amyloid cascade hypothesis

Answer 14

increased production or decreased degradation of A-beta

plaque formation

hyperphosphorylation of tau

neurofibrillary tangle formation

synaptic dysfuntion and neuron loss

memory loss and cognitive deficits

Question 15

What can be used to detect beta-amyloid in the brain nowadays?

Answer 15

PET scan with a radioactive tracer

Question 16

What biomarkers in the CSF can you use to diagnose Alzheimer’s?

Answer 16

low beta-amyloid 1-42 (being used up in the formation of plaques)
high total tau protein (neurons are lysing and releasing tau)
elevated phosphorylated tau

Question 17

T/F: The amyloid beta and tau CSF tests are not fully conclusive, because normal elderly individuals have amyloid plaques and tau neurofibrillary tangles, too

Answer 17

true

Question 18

Signs and symptoms of Parkinson’s disease?

Answer 18

tremor
rigidity
masked facies
stooped posture
arms, elbows, wrists, hips, knees slightly flexed
shuffling steps

Question 19

How does Parkinson’s differ from Alzheimer’s?

Answer 19

Parkinson’s is a motor disease, which involves the basal ganglia!

**AD no motor symptoms really

Question 20

What is happening neurologically in Parkinson’s disease?

Answer 20

cell death of dopaminergic neurons in the SUBSTANTIA NIGRA, which control movement

Question 21

What is Parkinson’s treated with?

Answer 21

L-DOPA

Question 22

What comprises the Lewy body like inclusion bodies found in Parkinson’s disease?

Answer 22

alpha-Synuclein

Question 23

These patients present with dementia (like Alzheimer’s) then they develop Parkinsons

Answer 23

dementia with lewy bodies

Question 24

What is ALS?

Answer 24

upper and lower motor neuron disease

Question 25

What does amyotrophic refer to in ALS?

Answer 25

muscle atrophy, weakness, and fasciculations that signify lower motor neuron problems

Question 26

What does lateral sclerosis refer to in ALS?

Answer 26

hardness to palpation of the lateral columns of the spinal cord, bc gliosis follows degeneration of the corticospinal tracts

Question 27

Symptoms of ALS are primarily those of (blank)

Answer 27

weakness

Question 28

What happens in ALS?

Answer 28

wallerian degeneration and gliosis leads to lateral sclerosis

Question 29

Loss of lower motor neurons results in (blank)

Answer 29

denervation muscle atrophy

**these patients waste away, they can’t eat or talk, etc

Question 30

How do patients with ALS die?

Answer 30

their intercostal muscles atrophy and they die of respiratory distress or pneumonia

Question 31

What is causing ALS?

Answer 31

mutated superoxide dismutase; this aggregates and causes too much glutamate release and excitotoxicity

Question 32

What drug is used to treat ALS? What does it do?

Answer 32

riluzole; inhibits glutamate release and blocks post-synaptic actions of NMDA receptors

**decreases excitotoxicity

Question 33

What is Syndenham’s chorea?

Answer 33

involuntary movement in children; associated with post-streptococcal disease

Question 34

What is Huntington’s chorea?

Answer 34

hyperkinetic movement disorder

Question 35

Huntington’s disease affects the (blank)

Answer 35

striatum (basal ganglia)

Question 36

What happens to the ventricles in Huntingtons disease?

Answer 36

enlarged ventricles because caudate and putamen are atrophied

Question 37

What is wrong genetically in Huntington’s disease?

Answer 37

the Huntington’s disease gene has too many CAG trinucleotide repeats which codes for glutamine; leads to long protein aggregates

**if it’s longer, it will occur at a younger age

Question 38

What happens when the long CAG repeat proteins aggregate?

Answer 38

they form inclusions in the nuclei

Question 39

T/F: Huntington’s disease is passed from generation to generation.

Answer 39

True