Neurotrophins

Question 1

What are neurotrophins?

Answer 1

Factors which influence neuronal/ synapse survival

Question 2

How was NGF discovered?

Answer 2

Discovered when a sarcoma was transplanted into a developing chick embryo- axons started to grow in/through the tumour
NGF also found in snake venom

Question 3

What is the ratio of subunits in the NGF structure

Answer 3

alpha:beta:gamma
2:1:2
Beta is the only active subunit in the complex

Question 4

Describe retrograde transport of NGF

Answer 4

1. NGF bind to receptor
2. NGF+receptor internalised
3. transported to the soma

Question 5

What receptors do NGF bind to with high and low affinity? And what are the effects

Answer 5

HIGH= TrkA- affects differentiation, growth and movement

LOW=p75- NTR- promotes cell death OR survival depending on the context

Question 6

How do axons change their dependency on specific NTS?

Answer 6

Arrival at their target- often coincides with new expression of NTs by the target
E.G- early in developent NT3 can support many neuron types

Question 7

What are 3 examples of Neurotrophins

Answer 7

1. BDNF
2. NTF3
3. NT4

Question 8

Example of another NT family

Answer 8

Glial derived neurotrophic factors

Question 9

3 examples of a cytokine

Answer 9

1. Ciliary NTF
2. Hepatocyte GF
3. Macrophage stimulating protein (MSP)

Question 10

What else are NTs important or

Answer 10

1. Formation of the monosynaptic stretch reflex

2. Determination of dendritic morphology and connectivity

Question 11

What is the primary determinant of survival of neurons/synapses?

Answer 11

Co-ordinated electrical activity pre and post synaptically

Question 12

What happens if there is deliberate non-coordinated firing?

Answer 12

Increased synapse loss

Question 13

What is neuron survival correlated to?

Answer 13

The amount of target tissue

Question 14

Summary of the intrinsic pathway of apoptosis

Answer 14

DNA damage & P53
Damaged mitochondria releases cytochrome c
initiator caspase 9 activated
effector caspase 3 activated

Question 15

Summary of the extrinsic pathway of apoptosis

Answer 15

Death ligands (fas)
Death receptors (fas)
Cleavage and subsequent activation of initiator caspase 8

Question 16

What does effector caspase 3 do

Answer 16

Cleaves proteins involved in:

1. Inhibiting apoptosis
2. DNA repair
3. cell cycle
4. nuclear structure

Question 17

Which genes do C.Elegans need both of to survive?

Answer 17

ced-3 and ced-4

Question 18

What can N.Ts do

Answer 18

Give pro and anti apoptotic signals

Question 19

What does BDNF activation of P75-NTR cause?

Answer 19

Apoptosis

Question 20

What also activated P75-NTR?

Answer 20

Pro-NGF

Question 21

What are the 2 pathways associated with BDNF release

Answer 21

1. Regulated pathway (proBDNF pound to CPE)

2. Constitutive secretory pathway (proBDNF bound to sortilin)

Question 22

What stimulates the release of NT into a synapse?

Answer 22

Calcium influx- due to depolarisation

Question 23

What does increased the NMJ cause

Answer 23

More neuronal survival- polyneuronally innervated muscles

Question 24

What converts electrical activity into survival?

Answer 24

In the neuron where proBDNF is converted into BDNF- this neuron will survive

Question 25

How is electrical activity related to target tissue mass?

Answer 25

If presynaptic activity is blocked-
More neuronal projections-
More trophic factors
More survival