Neurotrophins Flashcards
What are neurotrophins
Extracellular molecules that enhance the survival of neurons
What was the result of grafting a limb bud from one chick onto another
Chick with missing limb had fewer neurons/synapses
Chick with extra limb had more DRG/synapses
amount of target is proportional to the amount of synapses formed
How was nerve growth factor discovered
Sarcomas implanted from mouse to chick embryo
This stimulated the growth of axons inside the chick
Even happened when they weren’t in direct contact suggesting the factor was a diffusible one
What is the structure of nerve growth factor
alpha2 beta gamma2
How was the action of NGF investigated
Campenot chamber - If NGF was present in any chamber the neurons survived
If it was only present in the centre the axons retracted from the edges
What are the two types of NGF receptor
- Tyrosine receptor kinase - high affinity - ligand induced dimerization followed by downstream phosphorylation
- p75-NTR - Low affinity - can relay a survival or cell death signal depending on the cellular context and the ligand that has bound
How dependency change as neurons grow
New born neurons may have no dependency
NT-3 can support many neuron types early in development
Arrival at target often coincides with a change in dependency and new expression of NT by the target cells
Trigeminal neurons - start - BDNF NT-3
Finish NGF and MSP
Why was the cytokine LIF, IL-6 and CNTF given optimism in becoming a neurodegenerative disease treatment
Because cutting the motor neurons during development of a limb causes neurons to die - if treated first with the cytokine the number of dead neurons were reduced.
