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neuroscience > Neurodegeneration > Flashcards

Neurodegeneration Flashcards

1
Q

what is neurodegeneration?

why is this a problem?

what is the biggest risk factor for most common neurodegenerative diseases?

A

progressive loss of neurones beyond that of the normal ageing process

neurones cannot be replaced

age

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2
Q

when does neurodegeneration occur?

A

neurodegenerative diseases e.g. Alzheimer’s

cancer
trauma (head/spine injury)
viral diseases
vascular/circulatory disorders

developmental disorders

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3
Q

what are the 3 examples of neurodegeneration-associated vascular and circulatory disorders?

A

ischemia/infarction

transient ischemic attacks

haemorrhage

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4
Q

what are the various causes of stroke?

A

atherosclerosis
= narrowing of vessels

thrombosis
= damages vessels

embolism
= a blockage e.g. plaque/air bubble

vasospasm
= abnormal contractions cause vessel rupture

hypertensive vasculopathy

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5
Q

2 types of stroke

A

ischemic
- clot blocks blood flow to brain
= deprives neurones from nutrients + O2 etc

haemorrhagic
- bleeding occurs inside/around brain tissue
= can cause destruction of neurones

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6
Q

what is venous infarction?

what does it result from?

risk factors?

A

a haemorrhagic stroke form

venous sinus thrombosis

no. of states that result in hyper viscosity or increased coagulability

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7
Q

topography of focal ischemia

A

focus = area where neurones begin to die via necrosis

flow gradient:
densely ischemia region surrounded by areas of less severe CBF (cerebral blood flow) reduction

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8
Q

how can necrotic cells at a focus affect surrounding cells?

what is this called and what does it lead to?

A

cells break open and release contents
-> e.g. release glutamate
-> glutamate toxicity
= kills other cells

ischemia penumbra
- an area of reduced perfusion sufficient to cause reversible clinical deficits
= can be reversed by quick intervention

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9
Q

what is an infective disease that causes neurodegeneration?

what are the different forms?

A

meningitis

bacterial
tuberculous
fungal
viral

inflammation of the coating of the brain containing the meninges

  • > can damage blood supply
  • > damages brain
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10
Q

what is poliomyelitis caused by?

what can it lead to?

A

poliovirus (RNA virus)

3% of cases enter the CNS

1% of cases this leads to focal loss of motor neurones in the spinal cord

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11
Q

what neuroscience findings have been discovered from polio?

A

study of spinal motor neurone loss + comparison to resulting loss of muscle control

-> mapping of motor neurone foci in the spinal cord to innervated muscle

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12
Q

what makes neurodegenerative diseases special?

A

often unknown cause

no cure

progressive

sporadic +/or inherited forms

often age dependent

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13
Q

types of neurodegenerative diseases

A

dementia

  • Alzheimer’s = most common
  • Prion = rare

movement disorders
- Parkinson’s
= loss of dopaminergic cells
- Huntingtons

Motor neurone disease
- ALS
- MS
loss of upper + lower motor neurones

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14
Q

what are Amyloidogenic diseases?

examples

A

neurodegenerative diseases where there’s deposition of an abnormal amyloidogenic protein isoform

Alzheimer’s disease
Parkinson’s disease
Prion disease

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15
Q

what are amyloidogenic proteins?

A

those that form fibrillar aggregates with beta-sheet configurations

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16
Q

Alzheimer’s disease facts

A

most common neurodegenerative disease

most common cause of dementia

chances increase with age
- 47% if over 85yrs

17
Q

Alzheimer’s potential causes

A

deposition of beta-amyloid
- amyloid cascade hypothesis

deposition of phosphorylated tau in the form of paired helical filaments or tangles

metal hypothesis
e.g. iron and copper become more highly concentrated in the brain in ND diseases

18
Q

Amyloid cascade hypothesis

A

no plaque:
APP broken down by alpha-secretase into beta-amyloid

plaque formation:
APP cleavage in a different location by beta-secretase
= forms amyloid plaques

19
Q

Formation of tau tangles

A

Tau proteins aggregate and can no longer bind to microtubules

  • > deposited
  • > damage neurones
20
Q

Parkinson’s disease facts

A

2nd most common ND disease
(1 in 200 over 50yrs)
NOT a dementia

changes in movement
resting tremor
difficulty in starting movement

21
Q

Parkinson’s disease cause

A

Due to loss of dopaminergic neurones
in the substantia nigra

loss of pathway with the striatum
-> removes inhibitory pathways
= misbalance in movement pathways

22
Q

causal genes for familial forms of Parkinson’s disease

A

PARK1
= alpha-synuclein protein which is usually deposited as the aggregating protein in PD

PARK2
= Parkin associated with breaking down protein via UPS (ubiquitin-proteasome} pathway

PARK8
= LRRK2 associated with phosphorylation of proteins affecting the rate of protein breakdown

23
Q

Prion diseases facts

A

v rare

transmissible (experimentally)

human and animal diseases

sporadic or inherited

e.g. Kuru from eating human brain
vCJD

24
Q

Prion disease characteristics

A

long incubation period
(10-40yrs in humans)

deposition of large amounts of abnormal prion protein

rapid neuronal loss
gliosis = proliferation of glial cells
formation of small vacuoles

short symptomatic period before death

25
Q

prion protein misfolding

A

normal protein has a helical structure

when misfolded:
takes on beta-sheet structure
-> can aggregate
-> initiate neurone death

once substantial amount made (during long incubation period)
-> can catalyse own misfolding

26
Q

metal hypothesis

A

in each case (Alzheimer’s, Parkinson’s, Prion)
the normal protein is associated with binding a protein e.g. copper

suggests metals play some role

27
Q

2 diseases of myelin

A

demyelinating diseases
- acquired disorders of myelin e.g. multiple sclerosis

dysmyelinating diseases

  • genetic disorders destroying myelin during its formation
    e. g. leukodystrophies
28
Q

demyelinating diseases

A

axons are myelinated and later destroyed

via immune cell invasion theory

29
Q

multiple sclerosis facts

A

most common disease of CNS myelin

1:1000

progressive with relapsing + remitting accumulations of focal neurologic deficits

cause thought to be autoimmune

30
Q

MS symptoms

A

muscle weakness

ataxia (difficulty moving)

difficulty with speech + swallowing

31
Q

immune cell invasion MS theory

A

invade spinal cord

trigger immune response against myelin

cells (e.g. microglia) become activated and either cause destruction of oligodendrocytes (which repair damaged myelin) or destroy myelin sheath directly

neuroscience (17 decks)

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