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ANAT 242 > L11 > Flashcards

L11 Flashcards

1
Q

what are 2 pathological hallmarks of AD

A

plaques and tangles

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2
Q

what does amyloid precursor protein usually get cleaved by

A

alpha and gamma secretase

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3
Q

what does amyloid beta do

A

This is toxic and it clumps together to form plaques. These kill all the cells around them (these are also toxic in their soluble form)

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4
Q

what happens to Tau in AD

A

TAU proteins usually stabilise microtubules.

These proteins become phosphorylated and then the microtubules fall apart and the TAU gets clumped together

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5
Q

what are the 3 stages of Tau mediated neurodegeneration

A
  1. Hyperphos of tau leading to disassembly of MTs causing axonal transport
    insufficiency
  2. Tau aggregates in
    axons/dendrites which congest axonal
    transport
  3. Tau pathology
    transmitted
    synaptically
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6
Q

describe the chronological relationships among Alzheimer’s disease
pathology and clinical symptoms

A

both Tau phosphorylation and beta amyloid start happening in the preclinical phase

however Tau phosphorylation starts happening before BA but happens slowly

BA generation happens latter but more rapidly

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7
Q

what are the similarities between AD and diabetic neuropathy

A

they both disrupt protein structure –

disrupt structure =
disrupt function causing clinical symptoms

once symptoms appear it maybe too late for recovery

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8
Q

what does the nissl stain, stain

A

rER (therefore soma in neurons)

Nissl was found to be selective for
RNA and so represents large stacks
of rough endoplasmic reticulum

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9
Q

what are proteins involved in, in neurons

A

axonal transport and phospholipid bilayer (the proteins in it)

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10
Q

describe the Phospholipid bilayer

A

hydrophobic ends in middle zone

hydrophilic ends –intra/extracellular
compartment

!not permeable to ions!
- it is this reason that neurons have so many proteins as the need so many ion channels

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11
Q

what are the 2 types of channels

A

a simple channel

a complex folded structure composed of subunits (same/different)

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12
Q

all cells have proteins in the membrane. why in neurons do they produce significantly more than other cells

A

neurons have a huge membrane area

´Epithelial cell

  • 20µm soma diameter
  • membrane area 1,256µm2

neuron
- 20µm soma diameter
- membrane area 250,000µm2
therefore it is 200x greater membrane area

to make these proteins there is lots of RER

also have specialised vesicles

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13
Q

why are membrane proteins are essential components of

neuronal structure

A
  • are essential for neuronal function therefore proteins need to be in the ‘right’ place and any change may result in dysfunction
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14
Q

what hold the transmembrane protein in the correct place in the membrane

A

Transmembrane protein –> scaffolding protein –> actin mesh

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15
Q

what technique is used to identify and locate proteins

A

immunohistochemistry

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16
Q

what does immunohistochemistry tell us

A

where the protein is, where it is held/located (cellular level)

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17
Q

how does immunohistochemistry work

A

first you would take a protein of interest from a rat and inject it into a goat. The goats immune system would then produce antibodies to this foreign object (protein of interest). This is called the primary antibody

We then produce a secondary antibody which is just a generic goat antibody (because the primary is specific to the protein of interest so we don’t know what it is made up of. The secondary we do therefore we are able to produce a morker to see the secondary antibody

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18
Q

what is the point of the primary antibody when we have the secondary antibody

A

We don’t just send the general goat antibody (secondary) because the protein of interest might be in a hard place to get to therefore you want a specific antibody to be produced so that it is alse to reach it.

The second reason why we do it this way is so that we can amplify the signal

19
Q

what is ankG

A

it is a scaffolding protein in the proximal axon and nodes

20
Q

what is Caspr

A
  • transmembrane protein
  • member of neurexin family
  • cell adhesion

This is in very specific locations

21
Q

what is MAP2

A
  • microtubule associated protein
  • absent in most astrocytes

MAP 2 is specific for dendrites

22
Q

what is PO

A
  • Myelin protein
23
Q

why is actin often yellow in immunohistochemistry

A

Dendritic spine morphology (green)

F-actin (red)

Merged red and
green are shown in yellow.

because actin is what is in the dendritic spines

24
Q

why do we want to know protein location

A

because it helps to understand their function

25
Q

why do we use immunohistochemistry

A

Using Immunohistochemistry we can identify multiple proteins in
multiple locations -> precision of function and a range of
functions

26
Q

what is found at a chemical synappes

A

presynaptic = specialised membrane with active zones where neurotransmitter is released

cleft = matrix fibrous proteins

postsynaptic = specialised membrane with receptors for neurotransmitters

therefore the synapse is a complex membrane specialisation

27
Q

what does the presynaptic membrane contain

A
  • Calcium channels
  • Docking proteins
  • Transporter proteins
  • Reuptake transporter
  • Specific vesicle proteins
28
Q

what does the postsynaptic membrane contain

A

Voltage gated channels

Transmitter-gated ion channels

29
Q

what is an example of why we have postsynaptic densities

NMDA receptor

A

NMDA receptor- transmitter gated ion channel

it has a complex protein - post synaptic density

PSD-95 - scaffold protein, under the plasma membrane for the clustering of receptors, ion channels etc.

30
Q

what are some examples of cleft proteins

A

Trans-synaptic proteins

Mind the gap (MTG) - binding protein

cell adhesion molecules

31
Q

where is mind the gap protein secreted from

A

Secreted presynaptically and crosses the gap to the post synaptic density

32
Q

what do cell adhesion molecules interact with

A

interact with molecules on

surface of adjacent cell

33
Q

why do we have local protein synthesis

A

because if everything was made in the soma and then transported down the axon (anterograde by kinesin) then it would take forever

34
Q

where does local protein synthesis happen

A

at the post syanptc membrane

35
Q

how does local protein synthesis happen

A

The repressed mRNA gets attached onto the motor protein and via kinesin it is attached to the actin network and is transported to where it needs to go

the mRNA then goes to the polyribosomes which make the protein

36
Q

what is Fluorescence in situ hybridization (FISH)

A

you insert a florescent probe which is complimentary to the sequence of interest

then you can see where the protein is being made showing the localization of
the mRNA at presynaptic sites,

37
Q

what can identify newly synthesised proteins form mature proteins

A

PLA labeling

38
Q

how many synapses are there in dendrites per micrometer

A

4

39
Q

how many receiving synapses per neuron

A

10,000

40
Q

how many output synapses per neuron

A

100,000

41
Q

why do we have local protein synthesis

A

morphological complexity, the volume, and the capacity of the neurons

Remember it takes a day to get from the soma to the axon therefore we need local protein synthesis

Therefore it is about getting that processing of information within minutes not hours/days

42
Q

how many different proteins are there at a synapse

A

2500

43
Q

why does the brain use so much energy

A

because of the protein demand

ANAT 242 (17 decks)

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