Neurotrophins Flashcards
What are neurotrophins?
Factors which influence neuronal/ synapse survival
How was NGF discovered?
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
What is the ratio of subunits in the NGF structure
alpha:beta:gamma
2:1:2
Beta is the only active subunit in the complex
Describe retrograde transport of NGF
- NGF bind to receptor
- NGF+receptor internalised
- transported to the soma
What receptors do NGF bind to with high and low affinity? And what are the effects
HIGH= TrkA- affects differentiation, growth and movement
LOW=p75- NTR- promotes cell death OR survival depending on the context
How do axons change their dependency on specific NTS?
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
What are 3 examples of Neurotrophins
- BDNF
- NTF3
- NT4
Example of another NT family
Glial derived neurotrophic factors
3 examples of a cytokine
- Ciliary NTF
- Hepatocyte GF
- Macrophage stimulating protein (MSP)
What else are NTs important or
- Formation of the monosynaptic stretch reflex
2. Determination of dendritic morphology and connectivity
What is the primary determinant of survival of neurons/synapses?
Co-ordinated electrical activity pre and post synaptically
What happens if there is deliberate non-coordinated firing?
Increased synapse loss
What is neuron survival correlated to?
The amount of target tissue
Summary of the intrinsic pathway of apoptosis
DNA damage & P53
Damaged mitochondria releases cytochrome c
initiator caspase 9 activated
effector caspase 3 activated
Summary of the extrinsic pathway of apoptosis
Death ligands (fas) Death receptors (fas) Cleavage and subsequent activation of initiator caspase 8
What does effector caspase 3 do
Cleaves proteins involved in:
- Inhibiting apoptosis
- DNA repair
- cell cycle
- nuclear structure
Which genes do C.Elegans need both of to survive?
ced-3 and ced-4
What can N.Ts do
Give pro and anti apoptotic signals
What does BDNF activation of P75-NTR cause?
Apoptosis
What also activated P75-NTR?
Pro-NGF
What are the 2 pathways associated with BDNF release
- Regulated pathway (proBDNF pound to CPE)
2. Constitutive secretory pathway (proBDNF bound to sortilin)
What stimulates the release of NT into a synapse?
Calcium influx- due to depolarisation
What does increased the NMJ cause
More neuronal survival- polyneuronally innervated muscles
What converts electrical activity into survival?
In the neuron where proBDNF is converted into BDNF- this neuron will survive
How is electrical activity related to target tissue mass?
If presynaptic activity is blocked-
More neuronal projections-
More trophic factors
More survival
