Neurotoxic Mechanisms

Question 1

Define:
-neurotoxicity
-neurotoxins
Where can neurotoxins be acquired from?

Answer 1

Lecture 5, slide 2

Question 2

Briefly describe the structural organisation of the nervous system?

Answer 2

Lecture 5, slide 4-5

Question 3

Give examples of glial cells and their role

Answer 3

Lecture 5, slide 6

Question 4

What is the blood brain barrier?

Answer 4

Lecture 5, slide 10-11

Question 5

What are the pathways for transport across the BBB?

Answer 5

Lecture 5, slide 12

Question 6

Why is the nervous system particularly susceptible to damage?

Answer 6

Lecture 5, slide 13

Question 7

What can cause the BBB to break down?

Answer 7

Lecture 5, slide 14

Question 8

What are the causes of neurotoxicity?

Answer 8

Lecture 5, slide 15

Question 9

What are some routes of exposure to neurotoxins?

Answer 9

Lecture 5, slide 16

Question 10

What are the different types of neurotoxic injury?

Answer 10

Lecture 5, slide 17

Question 11

Give examples of neurotoxins that can cause each type of neurotoxic injury.

Answer 11

Lecture 5, slide 18

Question 12

Give examples of neurotoxins that target ion channels

Answer 12

Lecture 5, slide 19

Question 13

Discuss snake venom as a neurotoxin

Answer 13

Lecture 5, slide 20

Question 14

Discuss lead as a neurotoxin

Answer 14

Lecture 5, slide 21-24

Question 15

Give examples of CNS diseases

Answer 15

Lecture 5, slide 25

Question 16

Give examples of neurodegenerative diseases, their pathology and the proteins that are involved in them.

Answer 16

Lecture 5, slide 27

• Alzheimer’s disease
• Parkinson’s disease
• Prion diseases

Question 17

What are lysosomal storage diseases? Give examples of lysosomal storage diseases (LSD), their pathology and the major ‘storage’ materials involved

Answer 17

Lecture 5, slide 28

• Tay-Sachs disease
• Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies.

Question 18

What is CNS inflammation a hallmark of? How is it caused and what does it lead to?

Answer 18

Lecture 5, slide 29

Question 19

What are the hallmarks of Alzheimer’s Disease (AD) pathology?

Answer 19

Lecture 5, slide 31

Question 20

Discuss the different hypotheses for AD?

Answer 20

Lecture 5, slide 32-33

Question 21

How do neurofibrillary tangles form?

Answer 21

Lecture 5, slide 34-35

Question 22

Give examples of organs affected in disorders of lysosomes and lysosome related organelles (LRO)

Answer 22

Lecture 5, slide 37

Question 23

What has the studying of disorders of lysosomes and LROs uncovered?

Answer 23

Lecture 5, slide 38-40

Question 24

What can clinical symptoms of LSDs include?

Answer 24

Lecture 5, slide 41

Question 25

What are threshold effects in neurodegenerative diseases?

Answer 25

Lecture 5, slide 42

Question 26

What is excitotoxicity? What is the hypothesis behind it? What can cause it?

Answer 26

Lecture 5, slide 43-45

Question 27

How can acute excitotoxic shock be treated?

Answer 27

Lecture 5, slide 46

Question 28

Give examples of diseases potentially involving excitotoxicity

Answer 28

Lecture 5, slide 47

Question 29

Discuss the specificity of NMDA-induced excitotoxicity.

Answer 29

Lecture 5, slide 51-52

Question 30

How may diseases lead to neurotoxicity via glutamate?

Answer 30

Lecture 5, slide 53

Question 31

Give examples of excitotoxins. What do excitotoxins cause?

Answer 31

Lecture 5, slide 54

Question 32

Give MPTP as an example of a neurotoxin.

Answer 32

MPTP is a neurotoxin that causes neuronopathy and its injection can lead to the onset of Parkinsonian symptoms. Once MPTP crosses the blood-brain barrier, it is metabolised into MPP+ by the monoamine oxidase B of astrocytes. MPP+ interferes with complex I of the respiration electron transport chain and this causes the build-up of free radicals, leading to cell death. Specifically, the death of dopaminergic cells in the pars compacta of the substantia nigra.

Question 33

Give acrylamide as an example of a neurotoxin

Answer 33

Acrylamide is a neurotoxin that causes myelinopathy and is a particular concern in factories. Especially vulnerable neurons are the sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads. Studies have shown that acrylamide could adduct cysteine residues on presynaptic proteins that are involved in membrane fusion processes. It may also lead to inhibition of neurotransmitter release and alter cytoskeleton protein levels.