L8: Axon regeneration and mechanisms Flashcards
What are 4 goals of regenerative neuroscience?
- Inhibit scar formation
- Reduce inhibition of regeneration
- Promote regenerative molecules
- Replace cell loss
How do changes in Ca2+ influx affect axonal growth?
Influx activates kinases (PKA->ERK)
This has local effects on mRNA and retrograde transport to nucleus for axonal growth.
How is the transcriptional response modulated?
Rabs: NGF factors released and internalised into endosomes, retrograde transported with Rab7 & Rab5. These are partially degraded and contain kinases which activate and modulate transcriptional response.
How does DLK promote axonal growth?
Calcium influx activates DLK phosphorylation, retrograde transported to phosphorylate transcription factors e.g STAT3. This increases acetylation of chromatin and hence its accessibility to transcription factors to promote axonal growth.
Name 2 myelin associated molecules and their effect on regeneration.
NOGO and MAG.
Binds to NOGO receptor (NgR1) which activates RhoA GTPases, inducing ROCK & LIMK. This causes growth cone collapse.
What are CSPGs and how do they act?
Chondroitin sulfate proteoglycans. They bind to PTOσ, causing activation of RhoA, ROCK, LIMK.. This causes actin depolymerisation and therefore growth cone collapse.
Another molecule that leads to growth cone collapse?
Semaphorins
How is it possible to enhance regenerative potential?
Administer cAMP which activates PKA, which activating TFs including CREB for pro growth effects.
IL-6 binding causes STAT3 phosphorylation.
Delete PTEN, activates mTOR and increased protein synthesis.
What is the effect of the retinoic acid pathway?
Binds to RAR-B receptor, repressing expression of LINGO1. This reduces axonal collapse and inhibitory signalling.
Give an example of when PTEN deletion was used.
Rat optic nerve- lots of outgrowth linked to mTOR dependent local translation.
Which tract is the least able to regenerate?
Cortico-spinal
