Cell Death and Neurotrophic Factors Flashcards

1
Q

What are the features of apoptosis?

A

Nuclear condensation and fragmentation
Cytoplasmic blebbing - no cytoplasm release
Caspase activation - breakdown of nuclear lamina and cytoskeleton
DNA fragmentation

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2
Q

What are the steps of apoptosis?

A

Ion influx into mitochondria
Cytochrome C release from mitochondria - binds to Apaf1
Caspase9 activation
Caspase3 activation - hydrolyses substrates - degradation of cellular components
Cell death

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3
Q

Name 2 survival factors

A

Bcl-2

BclXL

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4
Q

Name 2 proapoptotic proteins and describe their function

A

Bax
tBID
Promote cytochrome C release

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5
Q

What is the effect of a caspase9 KO in an embryo?

A

No apoptosis - brain overgrowth

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6
Q

What is the effect of removing the target limb on MNs?

A

Decreases MN survival

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7
Q

What is the effect of grafting an additional limb bud to one side of embryo on MNs?

A

Increases MN survival

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8
Q

What is the effect of a single limb ablation on sensory neurons?

A

Decreases corresponding DRG neuron survival

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9
Q

What does the retrograde survival signal from the periphery to the cell body ensure?

A

Only healthy neurons innervate target

Size of innervation matches size of target

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10
Q

What type of molecule is nerve growth factor (NGF)?

A

Protein

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11
Q

What is the effect of NGF?

A

Promotes neuron growth and survival

Only on sympathetic and sensory neurons

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12
Q

What experimental technique can be used to show how retrograde signalling of NGF promotes cell survival?

A

Campenot chamber

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13
Q

What is the high affinity receptor for NGF?

A

TrkA

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14
Q

What is the high affinity receptor for BDNF, NT-4/5, and NT-3?

A

TrkB

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15
Q

What is the high affinity receptor for NT-3?

A

TrkC

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16
Q

What is the low affinity receptor for NGF?

A

p75

17
Q

What is the effect of p75?

A

Potentiates signalling via TrkA

Promotes apoptosis in absence of TrkA

18
Q

What type of receptor is TrkA?

A

Receptor tyrosine kinase

19
Q

Which enzymes are activated by TrkA activation and what are their effects?

A

PI-3 kinase - survival
Ras-MAP kinase - differentiation, axonal and dendritic growth
Phospholipase C-γ - synapse function

20
Q

Describe the process of cell survival by NGF

A
NGF activates TrkA
PI-3 kinase activation
Akt activation
Bad phosphorylation
Phospho-Bad sequestered by 14-3-3 - prevents binding to Bcl-2 and Bcl-XL - prevents opening of Bax ion channels