Neurodegeneration 2

Question 1

Two main theories of the cause of alzheimers?

Answer 1

Deposition of beta-amyloid protein (amyloid cascade hypothesis) or deposition of phosphorylated tau in the form of helical filaments or tangles

Question 2

Third theory of cause of alzheimers?

Answer 2

Metal hypothesis

Question 3

Function of amyloid precursor protein?

Answer 3

Unknown, possibly ion transport and memory

Question 4

What happens to beta amyloid protein when it is broken down by the cell?

Answer 4

It is acted on by secretases

Question 5

Which secretases can act on amyloid precursor protein?

Answer 5

alpha or beta

Question 6

Which secretase acts most commonly on APP?

Answer 6

alpha

Question 7

Which products are formed if alpha secretase acts on APP?

Answer 7

Aicd, p3 (both are harmless)

Question 8

Difference between alpha and beta secretase pathway?

Answer 8

APP is cut at a different location

Question 9

How can gamma secretase influence the formation of plaques?

Answer 9

Where the gamma secretase cleaves at the C-terminal end

Question 10

At which AA position in the C terminal does gamma secretase cleave for beta amyloid aggregates to form?

Answer 10

42

Question 11

At which AA position in the C terminal does gamma secretase cleave for beta amyloid aggregates to not form?

Answer 11

40

Question 12

What causes parkinsons?

Answer 12

The loss of dopaminergic neurons in the substantia nigra

Question 13

Where does the substantia nigra usually innervate to?

Answer 13

Striatum

Question 14

What happens to striatum innervation from the substantia nigra in parkinsons?

Answer 14

It is lost–> cant control movement in the normal way

Question 15

Which proteins are involved in parkinsons?

Answer 15

Alpha synuclein (PARK1), Parkin (PARK2), DJ-1 (PARK7), PINK01 (PARK6), LRRK2 (PARK8), UCHL1 (PARK5)

Question 16

What are aggregates of alpha synuclein called?

Answer 16

Lewy bodies

Question 17

Are lewy bodies intra or extra cellular?

Answer 17

Intracellular

Question 18

Where are the cells containing lewy bodies found?

Answer 18

Substantia nigra

Question 19

WHat is Creutzfeldt-Jakob disease(CJD)?

Answer 19

Main form of human prion disease

Question 20

WHich disease results in animal models that replicate symptoms observed in humans?

Answer 20

Prion disease

Question 21

Characteristics of prion diseases?

Answer 21

long incubation period (10-40yrs), large deposits of prion protein, rapid neuronal loss, gliosis, vacuoles

Question 22

How does the prion protein misfold?

Answer 22

As a result of interaction with other misfolded prion proteins–> could by why it is transmissible

Question 23

Why is there a metal hypothesis regarding neurodegenerative diseases?

Answer 23

The proteins associated with NDs (APP, alpha synuclein, prion protein) are all metal binding proteins

Question 24

What are the two main families of demyelinating diseases?

Answer 24

Demyelinating diseases and dismyelinating diseases

Question 25

What is a demyelinating disease?

Answer 25

Myelin on axons is destroyed

Question 26

Most common demyelinating disease?

Answer 26

Multiple sclerosis

Question 27

What is a dismyelinating disease?

Answer 27

A disease where myelination doesnt occur normally

Question 28

Cause of multiple sclerosis?

Answer 28

CNS myelin is selectively destroyed–> axon is still there

Question 29

Onset of MS?

Answer 29

30-40

Question 30

Observable symptoms of MS?

Answer 30

Muscle weakness, difficulty moving (ataxia), difficulty speaking or swallowing