Neurotrophins Flashcards
e.g. of neurotrophins (and its receptors)
NGF (TrkA)
BDNF (TrkB)
NT-3 (TrkC)
NT4-5 (TrkB)
PC12
- tumour cell from adrenal medulla of kidney
- adding NGF, stop dividing and grow neurites (post-mitotic neuronal like)
- finding: identified receptor tyrosine kinase reacting with NGF (which was also found in superior cervical ganglion)
Continuation of PC12 research
Adding P140 to PC12 cells lead to growing neurites
What are two main types of neurotrophin?
1) cell survival
2) cell growth/branching
PI3k pathway can
both inhibit or initiate a pathway
Explain the 2 main pathway
PI3K(and Akt): cell growth
MAPK: cell survival; can be ERK (with CREB) or JNK
where ERK is programmed to live, JNK is programmed to die even with NGF
What are some components essential for apoptosis?
- Caspase (mouse) or CED3 (worm)
- Bax (mouse)
What are two main types of neurotrophin?
1) cell growth
2) branching
Explain relationship between MAPK and apoptosis
NGF binds MAPK pathway activation Activation of CREB by P Activated CREB initiate translation of BCL2 (anti apoptotic regulator) => apoptosis stops and cell lives
Explain the 2 main pathway
PI3K(and Akt): cell growth
MAPK: cell survival; can be ERK (with CREB) or JNK
TrkA activates…
binds: NGF
- MAPK
- SNT (important in neuronal differentiation)
- PI3K
Which neurotrophins are in charge of various receptor?
Nociceptor – NGF
Mechanorceptor – BNDF, NT3
Double faced side of P75 receptor
abundant but low affinity
- if pro-neurotrophin (precursor) binds, it kills it
- if mature neurotrophin binds, it has a positive survival effect
PI3k pathway can
both inhibit or initiate a pathway
Neurotrophic requirements for sensory neurons
NT4, BDNF, NGF
low-threshold
NT4: D-hair
Postnatal BDNF: RA and SA mechanoR
high threshold
embryonicNGF: Cmechanociceptor and C-mechanoheat nociceptor
PostnatalNGF: AM nociceptor