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Developmental Neurobiology > Neurotrophic factors > Flashcards

Neurotrophic factors Flashcards

1
Q

trophic functions

A

diffusible molecules derived from target cells that mediate long-term dependence between neurons and the cells they innervate (cell survival)

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2
Q

tropic functions

A

diffusible molecules derived from target cells that guide or orient the migration of other cells or cell processes (axons) towards targets (local)

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3
Q

types of neurotrophins

A

-NGF
-BDNF (brain derived neurotrophin factor)
-NT3/4

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4
Q

how are neurotrophins produced

A

proteolytic cleavage of proneurotrophins

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5
Q

what do proneurotrophins and mature neurotrophins bind to

A

low affinity receptor P75NTR

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6
Q

which high affinity Trk receptors do neurotrophins bind to

A

TrkA: NGF NT3

TrkB: NT3 BDNF NT4

TrkC: NT3

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7
Q

how are neurotrophins involved in signalling

A

neurotrophin dimers bring 2 RTK molecules close so their cytoplasmic TK cross phosphorylate (downstream signalling)

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8
Q

how do neurotrophins contribute to neuronal survival and differentiation

A

SOS/Ras/MAP3 Kinase activate gene transcription

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9
Q

how do neurotrophins inhibit apoptosis

A

Trk and Ras activate phosphatidylinositol 3 kinase (PI3K) and AKT inhibits apoptosis

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10
Q

what do neurotrophins regulate

A

dendritic morphologies
synapse development
synaptic plasticity

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11
Q

how does receptor binding induce cell survival

A

trk receptors are internalised from axonal membrane and transported to the cell body where changes in gene expression cause cell survival

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12
Q

what do neurons undergo

A

competition for neurotrophins
if not enough received - apoptosis

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13
Q

Trk receptor phosphorylation

A

tyrosine amino acids are phosphorylated
more active kinase domain phosphorylates responding signals

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14
Q

2 types of neurotrophin action

A

Fuzzy strategy (combinatorial effect) - correct

modular concepts

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15
Q

fuzzy strategy

A

a particular neurotrophic factor maintains more than one type of neuron

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16
Q

what is a modular concept

A

each neuron subtype has one individual neurotrophic factor

17
Q

what is huntington’s disease

A

autosomal dominant neurodegenerative disorder caused by expansion of 15 CAG repeats coding for Gln in particular proteins

18
Q

which amino acid is Gln

A

glutamine

19
Q

what is huntingtin (htt)

A

multifunctional proteins
20 residues of glutamine

20
Q

what produces BDNF

A

striatum

21
Q

what does HD cause

A

decreased antero/retrograde BDNF transport

22
Q

BDNF transport

A

anterograde transport of BDNF from cerebral cortex to striatum (BG)

23
Q

kinesins vs dynesins (motor proteins)

A

kinesins - anterograde transport
dyneins - retrograde transport

24
Q

what does BDNF transport require

A

BDNF adaptor
HAP-htt

HAP = htt associated proteins

25
Q

wt htt protein

A

neuronal survival by enhancing vesicle transport of BDNF/Trk along microtubules

26
Q

mutant htt

A

attenuated BDNF transport

27
Q

how do neurons attract axons

A

secreting BDNF at a gradient

28
Q

how is growth cone steering directed

A

local polymerisation

depolymerisation of underlying cytoskeleton

29
Q

post-translational processing of neurotrophins

A

proneurotrophins (low affinity for p75) converted to neurotrophins (high affinity for Trk)

via caspases (type of protease)

30
Q

pro-neurotrophins

A

-cell death
-LTD
-dendrite reduction
-axon branching supression
-activate p75NTR

31
Q

neurotrophins

A

cell survival
LTP
promotes dendrites
promotes axon branching - tropic effect reorients axons

32
Q

how is pre synaptic NT release increased

A

PLC pathway activated, increased Ca2+ conc
MAP phosphorylation of synapsin
Rab3 expressed

33
Q

post synaptic TrkB signalling

A

phosphorylation of voltage gated Na+/K+ channels and AMPA/NMDA receptor

AMPA receptor insertion

activation of TRP channels (Ca2+)/Rho GTPases/phosphatases - reducing GABA-R surface

local and global protein synthesis

34
Q

what is the neurotrophic hypothesis

A

survival of developing neurons depends on a supply of neurotrophic factor synthesis in limiting amounts in their target field

Developmental Neurobiology (19 decks)

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