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BMS3052 > Neurodegenerative conditions > Flashcards

Neurodegenerative conditions Flashcards

1
Q

Free radicals and ageing:

  • What are the two types of free radicals?
  • Endogenous sources of free radicals include
  • Exogenous sources of free radicals include
  • Two types of antioxidant defences:
A

Reactive oxygen species and reactive nitrogen species
Mitochondria, peroxidsomes, loxixygenases, NADPH oxidase, cytochrome P450
-UV light, ionising radiation, chemotherapy, inflammatory cytokines, environmental toxins
Enzymatic systems eg catalase, supraoxide dismutase, glutathione peroxidase
Non enzymatic systems eg. glutathione, vitamins (A, C, E)

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2
Q

Role of normal levels of free radicals?
Too little free radicals?
Too much free radicals?

A

Neuron development and function, LTP
Impaired cell proliferation and host defences
Random cellular damage, activation of certain signalling pathways –> cell death, disease and ageing

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3
Q

Why is the brain very sensitive to oxidative damage during ageing?

A

High metabolic demand

Low activity of antioxidative defence mechanisms

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4
Q

5 key hallmarks of ageing>

A 
Mitochondrial dysfunction 
Telomere attrition 
Epigenetic alterations 
Loss of proteostasis 
Deregulated nutrient sensing
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5
Q

2 aspects of mitochondrial dysfunction that lead to ageing

A

Reduced efficiency of complexes I and IV of electron transport chain
Mutations in mito DNA

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6
Q

3 reasons why the mitochondira are vulnerable to the effects of ageing?

A

Highly oxidative microenvironment

Lacks histones, and limited mito DNA repair mechanisms –> lack of protection against DNA damage –> ageing

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7
Q

Do telomeres shorten with age?

Are telomeres susceptible to age related deterioration?

A

Yes

Yes

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8
Q

During ageing,

  • Histones are ____
  • There is global ________
  • There is focal ______
A

Lost
hypomethylation
hypermethylation

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9
Q

Do epigenetic mechanisms protect from DNA damage?

Do abnormalities in histone modifying enzymes/chromatin remodelling lead to neurodegeneration?

A

Yes

Yes

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10
Q

2 ways ageing can contribute to epigenetic changes?

A

When mistakes in DNA rep occur, DNA repair proteins often need to remove epigenetic marks - which may not be replaced (correctly)
During DNA replication, epigenetic marks might not be copied correctly

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11
Q

What causes impaired protein folding?

A

Endogenous/exogenous stressors

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12
Q

What are the 4 ways that misfolded proteins are dealt with

A

Autophagy - macroautophagy and chaperone mediated autophagy
Proteasomal degradation
Chaperone mediated folding
Aggregation and ageing

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13
Q

During ageing, what happens to these pathways?

A

Autophagy and proteasomal degradation pathways are impaired –> more protein aggregation and ageing

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14
Q

Deregulated nutrient sensing - what two pathways and direction?

A

IGF1 and mTOR

Impaired –> extended lifespan

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15
Q

More info on deregulated nutrient sensing in notes?

A

Yes

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16
Q

4 other hallmarks?

A

Cellular senescence
Stem cell exhaustion
Altered intracellular communication
Genomic instability

17
Q

Are most neurodegenerative disorders sporadic, rather than genetic?

A

Yes

18
Q

4 sporadic and 2 genetic neurodegenerative diseases?

A

Alzheimers, Parkinson’s, ALS, Creutzfeldt Jakob disease

Huntington’s disease, spinal muscular atrophy

19
Q

Common features of neurodegenerative diseases?

A 
Delayed onsent
Most have unknown etiology  
Abnormal protein processing and aggregation 
Selective neuronal vulnerability 
Cellular toxic effects
20
Q

Pathogenesis features?

A 
Defective protein handling/degradation 
Accumulation of abberant/misfolded proteins 
Abberant epigenetic mechanisms 
Metabolic dysfunction 
Neuroinflammation
21
Q

More info on reactive microglia?

A

Yes

22
Q

Contrast dementia and mild cognitive impairment

A

Dementia is loss of memory plus other impairments, causes impared function in daily life
Mild cognitive impairment is loss of memory only, doesn’t cause impaired function

23
Q

Do notes have definition for MCI for American Academy of Neurology?

A

Yes

24
Q
A

Yes

25
Q

4? types?

A

Alzheimer’s
Vascular dementia
Frontotemporal dementia
Lewy body dementia

BMS3052 (15 decks)

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