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Disease, Diagnostics and Therapeutics > Neurological Disorders > Flashcards

Neurological Disorders Flashcards

1
Q

What are COMT inhibitors

A

A class of drug which inhibits the action of COMT, the enzyme involved in the degradation of levodopa.

They can help control symptoms between doses of L-DOPA and reduce the amount of L-DOPA needed.

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2
Q

What are anticholinergics

A

a class of drug which block the action of acetylcholine

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3
Q

True or false: neurons in the brain secrete their own serotonin.

A

true

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4
Q

What is the cheng-prusoff equation used for

A

The IC50 value is converted to an absolute inhibition constant Ki using the Cheng-Prusoff equation

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5
Q

Explain the steps of autophagy

A
  1. Cytosolic material is sequestered by an expanding membrane sac, the phagophore,
  2. Formation of a double-membrane vesicle, an autophagosome
  3. The outer membrane of the autophagosome subsequently fuses with a lysosome,
  4. Inner single membrane of the autophagosome exposed to lysosomal hydrolases
  5. The cargo-containing membrane compartment is then lysed
  6. Contents are degraded
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6
Q

What is pKi

A

The negative log of the Ki value (inhibition constant)

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7
Q

symptoms of alzheimer’s

A
  • loss of memory, cognitive ability, communication
  • changes in mood and personality
  • forgetting recent events, unable to store new information in the temporal lobe
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8
Q

What receptor activation inhibits noradrenaline release

A

presynaptic adrenergic receptors

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9
Q

where specifically is dopamine most abundant

A

corpus striatum

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10
Q

what is siRNA

A

Small interfering RNA, is the most commonly used RNA interference tool for silencing protein coding genes short-term; it induces genetic knock-down, of a variety of cell lines.

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11
Q

What is an IC50

A

The concentration of competing ligand which displaces 50% of the specific binding of the radioligand

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12
Q

What are the two strands of siRNA

A

anti-sense guide strand, and a sense strand

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13
Q

True or false: serotonin can cross the blood brain barrier

A

false

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14
Q

Explain the steps of apoptosis- extrinsic pathways

A
  1. Fas ligand binds to death receptors
  2. Protein recruitment and from death-inducing signalling complex (DISC)
  3. Activates caspase-8 initiator
  4. Activates caspase 3/7 executioner
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15
Q

what is the equation for radioligand equilibrium

A

kon = koff

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16
Q

What are MAO inhibitors

A

a class of drug which inhibit the activity of one, or both monoamine oxidases; both MAOs deaminate the neurotransmitter dopamine

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17
Q

What is L-DOPA

A

An anabolite for dopamine.

It can can cross the blood brain barrier and forms dopamine in the presence of DOPA decarboxylase

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18
Q

True or false: Deep brain stimulation destroys small sections of the patient brain, so is not reversible

A

False

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19
Q

why is L-DOPA used to treat parkinson’s

A

Dopmaine is hydrophilic so cant cross BBB

L-DOPA is take peripherally and can then cross the BBB where is it converted to dopamine

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20
Q

describe the nigrostriatal pathway

A

key dopamine pathway
cell body in the substantia nigra, moves up to corpus striatum
Involved in the production of movement, as part of the basal ganglia motor loop

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21
Q

What effect des Gs have

A

stimulate adenylyl cyclase to produce cAMP, increasing intracellular calcium among other cAMP mediated processes.

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22
Q

What is a radioligand binding assay

A

used to characterize the binding of a drug to its target receptor.

They can provide information on both the affinity and mode of interaction of the drug with its receptor.

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23
Q

true or false: Ki is an absolute value

A

true

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24
Q

Describe the tuberohypophyseal pathway

A

Dopamine release in this pathway is to inhibit prolactin release

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25
Q

How do Selective serotonin reuptake inhibitors work

A

increase the extracellular level of serotonin available for binding to the post-synaptic receptor

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26
Q

What are present to reduce likelihood of proteopathy

A

Chaperones- by avoiding the conformational change to beta-sheet structure.

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27
Q

symptoms of huntington’s

A

cognitive disorders - impulse control, task organisation. flexibilty, learning
movement disorder - involuntary jerking. twitching movements, rigidity, speech

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28
Q

How is dopamine broken down

A

broken down by homovanillic acid via DOPAC and 3MT

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29
Q

What is deep brain stimulation

A

A neurostimulator is implanted into the patient’s brain- subthalamic nucleus or Globus pallidus interna.

When switched on, the internal electrodes deliver high frequency stimulation to the targeted area, changing electrical signals which cause symptoms of diseases such as Parkinson’s.

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30
Q

What are anticholinergics used for

A

help to block involuntary muscle movements associated with disease, or in surgery to maintain body functions under anaesthetic

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31
Q

what is the precursor of noradrenaline

A

dopamine

32
Q

What is the precursor of dopamine

A

tyrosine

33
Q

what is huntingdons’ disease

A 
progressive neurodegeneration 
reduces lifespan (15-20yrs)
34
Q

What are antipsychotic drugs

A

These utilise the 4 dopaminergic pathways to reduce dopamine levels

35
Q

How can the availability of dopamine be increased in the brain

A

L-dopa , and DDC inhibitors that do not pass the BBB, such as carbidopa can increase its avaliability

36
Q

what type of molecules CAN cross the BBB

A

hydrophobic/non-lipophilic molecules

37
Q

What conditions are high dopamine associated with

A

paranoia or Schizophrenia

38
Q

Where is most serotonin found

A

in the raphe region, of the pons and upper brainstem

39
Q

What is a proteopathy

A

protein misfolding causing disease

40
Q

Describe the mesolimbic pathway

A

VTA –> Limbic system

41
Q

What neurotransmitter does cocaine modulate

A

dopamine

42
Q

what is MAO-B used for

A

used in the treatment of depression and parkinson’s

prevent the breakdown of dopamine

43
Q

how does siRNA elicit gene silencing

A

siRNA are transfected into cells, and the activated protein and nucleic acid complex binds to a single target mRNA sequence.

44
Q

Transmission of inherited genetic disorders with increased severity is called what

A

Anticipation

45
Q

70% of dopamine is found in which of the 4 pathways

A

Nigro-striatal

46
Q

What is noradrenaline

A

A post-ganglionic sympathetic neurotransmitter, and adrenoceptor agonist.

47
Q

Why are MAO inhibitors used to treat parkinson’s

A

by specifically targeting MAO-B. This prevents the dopamine catabolism associated with disease.

They can also block mAChR and inhibit glutaminergic NMDA receptors.

48
Q

true or false: focused ultrasound is non-invasive but irreversible

A

true

49
Q

What can tag histone proteins (epigenetic markers)

A

methyl, acetyl, ubiquitin, phosphate, and other biochemical groups.

50
Q

What is the cheese reaction

A

monoamine oxidase (MAO) effectively prevents dietary pressor amines, from entering the tissues.

So a hypertensive response can occur when subjects treated with MAO inhibitors ingest foods or beverages rich in such amines.

51
Q

What are epigenetic markers

A

Non-hereditary changes to the histone code or to any molecules other than the DNA itself, which include methylation of DNA and covalent modification of histone proteins

52
Q

What effect does Gi have

A

block the activity of adenylyl cyclase.

53
Q

what is the use of COMT

A

prevents L-DOPA being broken down into another dopamine precursor

54
Q

define bradykinesia

A

suppression of voluntary movement

55
Q

Which part of the pain control system does serotonin affect

A

the descending pain-control system

56
Q

Where is noradrenaline predominantly found in the brain

A

locus coeruleus, in the pons

57
Q

What is focused ultrasound

A

focuses beams of ultrasonic energy on targets deep within the brain, without damaging surrounding normal tissue.

It can temporarily open the blood-brain barrier, to improve delivery of genes, growth factors, stem cells, other drugs

58
Q

What is radioligand binding

A

Ligand and receptor remain bound for a length of time, dependent on the affinity of the drug for the receptor.

59
Q

What is dopamine

A

catecholaminergic neurotransmitter

60
Q

True or false: Some toxic mis-folds can interact with other native copies of the same protein and catalyse their conversion into the toxic state

A

true

61
Q

What is serotonin

A

A neurotransmitter derived from tryptophan

62
Q

What G protein uses D1 and D5

A

Gs

63
Q

what happens when misfolded or toxic proteins are identified?

A

They are tagged with ubiquitin and sent to the proteasome for degradation

64
Q

What G protein uses D2, 3 and 4

A

Gi

65
Q

What is the precursor to serotonin

A

tryptophan

66
Q

what proteins are proteopathies most likely to occur in

A

proteins containing repetitive amino acid motifs such as poly-glutamine (in Huntingdon Disease).

67
Q

What conditions are low dopamine associated with

A

Parkinson’s

68
Q

Explain the steps of apoptosis- intrinsic pathways

A
  1. Cytotoxic stress
  2. Translocation of pro-apoptotic Bcl-2 family to mitochondria
  3. Mitochondrial cytochrome C released
  4. Oligomerisation of pro-apoptotic factor Apaf-1, forms apoptosome
  5. Recruits caspase 9, which activates caspase 3
69
Q

what is alzheimer’s

A

progressive neurodegeneration

most common cause of dementia

70
Q

Where does epigenetic modification normally occur

A

N terminus of histone tails

71
Q

describe the mesocortical pathway

A

starts in VTA

through forebrain up to the cortex

72
Q

Why is L-DOPA often prescribed with a peripheral DOPA decarboxylase inhibitor (DCC)

A

It can also be converted to dopamine in the periphery- bad.

By increasing the concentration gradient between the brain and periphery, more dopamine becomes available in the brain.

73
Q

State the 5 dopaminergic receptors

A

D1, D2, D3, D4, and D5.

74
Q

Explain the steps of dopamine synthesis + release

A
  1. tyrosine is converted to DOPA
  2. DOPA is converted to dopamine in cytoplasm
  3. Dopamine transported into storage vesicles
  4. dopamine released into synaptic cleft
  5. dopamine reuptaken
  6. any remaining dopamine is destroyed by MAO or COMT
75
Q

what is the blood brain barrier

A

Several distinct barriers operating in parallel to restrict and regulate the passage of materials between the peripheral and cerebrospinal compartments

76
Q

What is an Ki

A

The inhibition constant for a drug

the concentration of competing ligand in a competition assay which would occupy 50% of the receptors if no radioligand were present.

77
Q

What is chaperone-mediated autophagy

A

chaperone complex delivers specific substrate proteins to lysosomes.

The substrate polypeptides are then translocated one by one through the lysosomal membrane protein and digested in the lysosomal lumen.

Disease, Diagnostics and Therapeutics (14 decks)

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