L15 AS

Question 1

What is the approx amount of developing neurons that die via programmed cell death PCD ?

Answer 1

50%

Question 2

what molecules are important for PCD?

Answer 2

neurotrophic factors

Question 3

what structures make NTFs?

Answer 3

target structures of axons

glial - astrocytes

Question 4

main way NTFs are transported ?

Answer 4

retrograde from target

Question 5

Whether the neuron has access to NTF or not dictates ?

Answer 5

if it dies or not

enough NTF = survival

Question 6

possible sources of NTF support ?

Answer 6

autocrine , paracrine 
extracellular 
target derived 
glial 
pathways 
afferent derived (DRG, sc)
systemically derived - hormones

Question 7

which was the first famil of NTF discovered ?

Answer 7

neurotrophins

Question 8

Neurotrophin family …

structure ?

Answer 8

BDNF
NGF
NT3/4

small basic homodimers

Question 9

what regions do neurotrophins have ?

Answer 9

homologus - conserved between members - cysteine knot (links dimers)

variable region - receptor binding

Question 10

what is NGF needed for ?

Answer 10

sympathetic neurons

Question 11

NGF is produced where ?

Answer 11

in tissues which require innervation by sym and sensory nerves

Question 12

what does NGF production cause

Answer 12

prevents programmed cell death, ↑ cell size, ↑ axonal

and dendritic outgrowth

Question 13

In the CNS NGF acts n the basal forebrain ?

Answer 13

ACH projections to hippo c neocortex

Question 14

BDNF support which neurons ?

Answer 14

sensory and parasym

Question 15

what does BDNF do ?

Answer 15

supports survival, growth and process outgrowth of
neurons in hipopocampus, basal forebrain, striatum,
retinal ganglion cells, some motor neurons

Question 16

BDNF KO ?

Answer 16

die within 2 weeks of birth

Question 17

NT3 located ?

Answer 17

in CNS - esp high in cortex, cerebellum , hippo c and thalamus

Question 18

what neurons is NT3 involved with ?

Answer 18

• acts on subpopulation of spinal motor neurons
• supports proprioceptive neurons in sensory ganglia
• sustains progenitor cells of neural crest
• critical for glial development

Question 19

NT3 KO

Answer 19

mice lack senory and propioceptive neurons

Question 20

NT4 KO

Answer 20

normal

functions overlap with other neurotrophins esp BDNF

Question 21

what receptors do neurotrophins bind to ?

Answer 21

Trk receptor family

p75 (low affinity receptor)

Question 22

Trk A,B,C bind what neurotrophins ?

Answer 22

A - NGF (NT3)
B - BDNF, NT4 (NT3)
C - NT3

Question 23

where are Trk receptors ?

Answer 23

on neurons at appropriate time in development

Question 24

Neurotrophin dimer binds to trk receptor monomer and then ?

Answer 24

pulls the other monomer in (receptor dimerisation)

Question 25

P75 located and function ?

Answer 25

along membrane of neuron needed for intracellular signalling to occur pulls trk receptor into them less affinty

Question 26

what is p75

Answer 26

member of TNF receptor family cytoplasmic domain - contains a “death” domain extracelular domain - ontains 4 cysteine-rich motifs

Question 27

Trk A expressed where on neuron ? | Describe domains ?

Answer 27

cell body and processes extracellular - contains 2 cysteine-rich clusters, 3 leucine-rich repeats, 2 Ig-like domains intracellular tyr kinase domain, and tyr docking-sites

Question 28

what happens to complex of TrkA NGF and p75

Answer 28

complex is internalised | → retrograde axonal transport to cell body

Question 29

where can proneurotrophins bind?

Answer 29

the p75 receptor not TRKs

Question 30

``` once Maturation through proteolysis of the proneurotrophins, each mature neurotrophin can bind and activate p75NTR, but exhibits more specific interactions with for ? ```

Answer 30

TRK

Question 31

NGF TRK A and P75 coplex binding parnters ?

Answer 31

sortilin, Nogo, Lingo 1

Question 32

mech of neurotrophin signalling ?

Answer 32

NTF binds dimerisation of Trk receptors → transphosphorylation of - two tyrosine residues in kinase domain - three other tyrosine residues formation of large signalling complexes (phosphorylation creates binding sites for proteins containing PTB or SH2 domains

Question 33

Intracellular pathways activated by neurotrphin signalling ?

Answer 33

Phospholipase C γ Phosphatidylinositol-3-kinase (PI-3K Ras

Question 34

PLC y

Answer 34

generation of DAG | and IP3 → PKC activation and Ca2+ mobilisation

Question 35

PI-3K

Answer 35

phosphoinositide production → activation of Akt kinase

Question 36

Ras

Answer 36

activation of MAP kinase cascades | eg. MEK-1/2→ERK-1/2