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BIOM2010 > Neurodegenerative Diseases > Flashcards

Neurodegenerative Diseases Flashcards

1
Q

How is Huntington’s disease passed on?

A

Autosomal dominant inheritance

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2
Q

List the Tx of Huntington’s disease

A

no cure so multidisciplinary care and management of disease Sx

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3
Q

In the progression of Huntington’s disease, what is generally the first to decline?

A

Functional abilities (can begin in the prodromal stages and leads to the motor diagnosis)

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4
Q

Which three signs and symptoms increase throughout the progression of Huntington’s disease?

A

motor impairment, cognitive impairment, chorea

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5
Q

Where in the world is the prevalence of Huntington’s disease increasing?

A

Western populations

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6
Q

What is the main pathological hallmark of Huntington’s disease?

A

degeneration and atrophy (size decrease) of the striatum (in the brain)

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7
Q

Which pathway is dysfunctional in Huntington’s disease?

A

Major stress response pathway

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8
Q

Which protein is ‘responsible’ for Huntington’s?

A

HTT

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9
Q

Cell autonomous and non cell autonomous death occurs in which neurodegenerative disease?

A

Huntington’s disease

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10
Q

Chorea is a symptom of Huntington’s disease and can be treated or managed with which drug?

A

Tetrabenazine

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11
Q

Explain the 2 mechanisms of action for Tetrabenazine and which condition it is contraindicated in

A
  1. Tetrabenazine binds to vesicles and prevents dopamine from entering them for release into the synapse
  2. Tetrabenazine competitively blocks dopamine binding to its receptors and passing an electric signal

Contraindicated in Parkinson’s disease

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12
Q

What is the experimental therapy being tested for HD?

A

prevent the translation of the HTT protein in the nucleus (changing the DNA)

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13
Q

Which neurodegenerative disease can be inherited or sporadic and which is more common?

A

Parkinson’s - more likely to be sporadic

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14
Q

Dopaminergic, non-dopaminergic drugs and deep brain simulation are treatments for which neurodegenerative disease?

A

Parkinsons disease

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15
Q

Which symptoms become apparent first in Parkinson’s disease?

A

Non-motor symptoms (sleep behaviour, depression, fatigue)

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16
Q

The diagnosis of Parkinson’s disease comes after the beginning of which type of symptoms?

A

Motor symptoms (tremor, rigidity, falls)

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17
Q

Is Parkinson’s disease more prevalent in men or women?

A

men

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18
Q

What are the pathological hallmarks of Parkinson’s disease?

A

loss of neurons in the substania nigra (SN) and widespread intracellular accumulation of alpha-synuclein

19
Q

Which feature is found in the limbic and neocortical regions as Parkinson’s progresses?

A

Lewy bodies

20
Q

What does the acronym TRAP stand for and which disease does it relate to?

A

Tremor at rest, rigidity of the limbs, Akinesia, Postural problems&raquo_space; Parkinson’s disease

21
Q

The loss of neurons in the SN leads to…

A

dopamine deficiency in the striatum

22
Q

What caused the increased actions of excitatory transmitters in Parkinson’s disease?

A

loss of inhibitory dopamine

23
Q

Dysfunction of the UPS and LAS systems is prevalent in which neurological condition?

A

Parkinson’s

24
Q

Which two drugs work outside the BBB on AADC which converts L-DOPA to dopamine?

A

Benserazide and Carbidopa

25
Q

Which endogenous molecule can be given as a drug to increase the production of dopamine in the brain?

A

L-DOPA (levodopa)

26
Q

List the MOA and target site of Pramipexole

A

MOA: dopamine agonist

Target site: D2 receptor

27
Q

List and briefly explain a non-pharmacological Tx for Parkinson’s disease

A

Deep Brain Stimulation

- high frequency stimulation of brain targets can alter neuronal circuits back to a more physiological state

28
Q

In general terms, when is the onset of Alzheimers and what is the average survival?

A

Around 60yrs old and average survival is 8-10 years

29
Q

While there is no cure for Alzheimers disease, which 3 components can be implemented in a patients life?

A

multidisciplinary care, management of disease Sx and treatment for co-morbidities

30
Q

Gene mutations are thought to be linked to which neurological diseases?

A

Alzheimers and ALS

31
Q

List the 5 elements of the disease progression (in the order which they occur) for Alzheimers.

A

Amyloid-beta plaques, tau-mediated neuron injury and dysfunction, brain structural changes, memory impairment, functional deficits

32
Q

Which neurological disease is one of the leading causes of death in Australia?

A

Alzheimers disease

33
Q

Explain the pathological hallmarks of Alzheimers disease.

A

The accumulation of Amyloid-beta plaques and Tau neurofibrillary tangles. In some cases, you may also see alpha-synuclein and TDP-43 pathology

There is cortical atrophy, medial temporal atrophy of the amygdala and hippocampus and loss of neuormelanin in the coeruleus

34
Q

What are the effects of Amyloid-beta?

A

APP is chopped by alpha or beta secretase that produces soluble fragments; simultaneous cutting leads to aggregates. This leads to cell autonomous and non-cell autonomous death

35
Q

What are the effects of Tau?

A

stabilises microtubules and their collapse leads to tau tangles which leads to cell autonomous and non-cell autonomous death

36
Q

Which Tx is used in Alzheimers which improves memory, attention, mood and behaviour?

A

Cholinesterase inhibitors which increase the concentration of ACh at the synapse

37
Q

What does ALS stand for?

A

Amyotrophic Lateral Sclerosis

38
Q

ALS is a type of which disease?

A

MND

39
Q

The degeneration of upper and lower motor neurons of the corticospinal tract os the pathological hallmark for which disease?

A

ALS

40
Q

ALS is a complex disease with multiple proposed pathogenic mechanisms. These mechanics are mostly linked to what and lead to what?

A

Gene mutations which lead to cell autonomous and non-cell autonomous

41
Q

Which two drugs are a proposed Tx for ALS?

A

Riluzole and Edaravone

42
Q

Describe the MOA of Riluzole? (3 points)

A

inhibition of glutamic acid release, inhibition of voltage gated sodium channels and blocking of excitatory amino acid transporters

43
Q

An experimental therapy states: Hyper metabolism in ALS is associated with….?

A

…greater functional decline and shorter survival

44
Q

Frontotemproal dementia can overlap with which neurodegenerative condition?

A

ALS

BIOM2010 (4 decks)

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