5/27- Degenerative Disorders Flashcards Preview

Term 5: Neuro > 5/27- Degenerative Disorders > Flashcards

Flashcards in 5/27- Degenerative Disorders Deck (48):
1

Symptoms seen with loss of cortical neurons?

Dementia

2

Symptoms seen with loss of basal ganglia neurons?

Movement disorder

3

Symptoms seen with loss of cerebellar neurons?

Ataxia

4

Symptoms seen with loss of motor neurons?

Weakness

5

What causes neuronal death in degeneration?

Diverse insults

Common final pathways (work in concert):

- Excitotoxicity

- Free radical injury

- Protein fibrillogenesis (extra/intracellular)

(Death via either necrosis or apoptosis)

6

Consequences of neuronal death (broad, 2)

- System dysfunction

- NT loss

7

What does it mean if cellular reaction to injury is "reactive"?

It can recover (Necrosis-Apoptosis-Reactive-Normal)

8

What is protein fibrillogenesis?

Protein misfolds and starts to polymerize/accumulate, aggregating into fibrils or filaments which may lead to cellular dysfunction or death

(early phases e.g. fibrils rather than inclusions are more destructive)

9

Types of protein fibrillogenesis?

May be:

- Extracellular protein deposit, "plaque"

- Intracellular protein deposit, "inclusion" (most intra are cytoplasmic, but some nuclear) (Innocent bystander proteins may be incorporated into fibrillization/inclusions)

10

How can fibrillogenesis be identified?

- Light or electron microscopy

- Immunohistochemistry for inclusions in nucleus/cytoplasm

11

What is the "stress protein"? What does it do?

Ubiquitin

Marks the misfolded protein for refolding or degradation by proteasome

12

What is a non-proteasome pathway for degradation of misfolded protein?

Autophagy by lysosomes

13

Composition of cytoplasmic inclusions?

Structural protein:

- Tau

- Synuclein

Stress protein:

- Ubiquitin

- Crystalline

- HSPs

14

Difference between structure and toxicity of fibrils vs. inclusions?

Fibrils: ultrastructural, nm, VERY toxic

Inclusions: light microscopy, um, less toxic

15

What is Tau protein? Causes what diseases?

Intracellular neuronal protein associated with microtubules

Causes "Tauopathies"

16

What is alpha-synuclein? Causes what diseases?

Intracellular neuronal and glial protein

Causes Lewy body disorders, e.g. Parkinson's

17

What is superoxide dismutase (SOD)? Causes what diseases?

Intracellular neuronal protein

Causes Familial ALS (can oxidize just fine, but protein misfolds and causes problems)

18

What is beta-amyloid? Causes what diseases?

Extracellular polymeration

Causes Alzheimer's Disease

19

T/F: Neuodegeneration is focal/localized? 3 examples?

False

Neurodegeneration may start focally and then spread

- Alzheimer's typ starts in hippocampus with memory problems (but may start in Broca's area with progressive aphasia)

- Parkinson's may start in 1 substantia nigra; hemikparkinsonism

- ALS may start focally (e.g. hand weakness on 1 side); as dz progresses, it spreads to other muscle groups

20

Three main steps in prion-like templating of neurodegeneration?

- Misfolding (stochastic, failure to degrade, or genetic propensity to misfold)

- Templating (misfolded pr modifies 2' structure of native protein in self-replicating cycle)

- Aggregation (misfolded prot tends to aggregate; IC = tangles)

21

Examples of overlapping neurodegenerative diseases (2)

- Parkinson's: dementia following movement disorder

- ALS: later frontotemporal dementia

22

What is a prion?

Misfolded protein that is so capable of modifying 2' structure of native protein in self-replicating cycle that it is INFECTIOUS

23

What is this?

Q image thumb

Cortical atrophy (caudate atrophy)

Can see hydrocephalus ex vacuo

24

What is this?

Q image thumb

Cortical atrophy: atrophic frontal/temporal lobes moreso than parietal/occipital

25

Which side is abnormal?

In what way?

Disease?

Q image thumb

Abnormal: right side

Problem: substantia nigra atrophy

Disease: Parkinson's disease

26

What are these histo pics of?

Which is abnormal?

Disease?

Q image thumb

Pictures of substantia nigra

Abnormal: right side

Problem: Parkinson's disease

27

What is shown in this picture?

Q image thumb

Lewy body in pigmented neuron in Parkinson's disease

28

What is the composition of Lewy bodies?

Extra or intracellular?

- Intracellular (cytoplasmic)

Strucutral protein: synuclein

Stress protein:

- Ubiquitin

- Crystalline

- HSPs

29

What is shown in this picutre?

Q image thumb

Cortical Lew bodies (a-Synuclein)

30

Most common causes of dementia (due to cortical degeneration)?

- Alzheimer's

- Pick's disease (frontotemporal dementia)

- Lewy body dementia (person with Parkinson's can develop this or vice versa, this can lead into Parkinson's)

31

Important pic

Q image thumb

KNOW THIS

32

Symptoms of Parkinson's disease (7)

- Cogwheel rigidity

- Resting tremor

- Bradykinesis

- Postural instability

- Clasp knife tonicity ?

(-masked facies)

(-en bloc turning)

33

Non a-synuclein misfolding (Lewy body formation) causes of Parkinsonism?

- Post-encephalitic Parkinsonism

- Progressive supranuclear palsy (tauopathy)

34

What is this? (pic 8)

Progressive supranuclear palsy (PSP)

35

What is this?

Q image thumb

Tau immunoreactive Globose Nueronal tangle in PSP (progressive supranuclear palsy)

36

What is multiple system atrophy (MSA)?

Degenerative dz with varying components of parkinsonism, cerebellar ataxia, and autonomic dysfunction once thought to be 3 separate diseases It is a synucleinopathy (a-synuclein); glial cytoplasmic inclusions, GCI

37

What is underlying mechanism of the different symptoms seen in MSA (multiple system atrophy)?

- Parkinsonism: striatonigral degeneration

- Ataxia: olivopontocerebellar degeneration

- Autonomic dysfct: Shy Drager dysautonomia

38

What degenerates in MSA?

- Substantia nigra

- Putamen

- Olivary nuclei

- Pontine nuclei

- Cerebellum

39

What does this show?

Q image thumb

Atrophy of pons in multiple system atrophy

40

What does this show?

Q image thumb

Alpha-synuclein positive inclusions in multiple system atrophy

41

What is Friedreich's ataxia?

What protein does it involve?

Most common hereditary ataxia

- Autosomal recessive

- GAA triplet repeat expansion (both alleles or one with expansion and other with mutation)

- Involves frataxin but NOT appeared to be a fibrillogenesis-related dz

- Results in loss of function

42

What organs does Friedreich's ataxia affect?

- CNS

- Heart

- Pancreas

43

What does this show?

Q image thumb

Cerebellar atrophy seen in Friedreich's ataxia and other spinocerebellar ataxias

44

What does this show?

Q image thumb

Friedreich's ataxia Multiple long tracts affected, including psinocerebellar

45

What does this show?

Q image thumb

Amyotrophic lateral sclerosis (ALS)

46

What parts of the SC are affected in ALS (tracts)?

- Corticospinal tract (lateral and anterior/ventral)

- Ventral horns

A image thumb
47

What does this show?

Q image thumb

Amyotrophic Lateral Sclerosis (ALS)

48

What causes ALS?

Familial forms from SOD1 (superoxide dismutase) mutations

Protein fibrils formal and damage cells (not a loss of free radical handling! Still functional)

Forms amyloid-like filaments and water-filled nanotubes