Neurotoxic Mechanisms Flashcards
Define:
-neurotoxicity
-neurotoxins
Where can neurotoxins be acquired from?
Lecture 5, slide 2
Briefly describe the structural organisation of the nervous system?
Lecture 5, slide 4-5
Give examples of glial cells and their role
Lecture 5, slide 6
What is the blood brain barrier?
Lecture 5, slide 10-11
What are the pathways for transport across the BBB?
Lecture 5, slide 12
Why is the nervous system particularly susceptible to damage?
Lecture 5, slide 13
What can cause the BBB to break down?
Lecture 5, slide 14
What are the causes of neurotoxicity?
Lecture 5, slide 15
What are some routes of exposure to neurotoxins?
Lecture 5, slide 16
What are the different types of neurotoxic injury?
Lecture 5, slide 17
Give examples of neurotoxins that can cause each type of neurotoxic injury.
Lecture 5, slide 18
Give examples of neurotoxins that target ion channels
Lecture 5, slide 19
Discuss snake venom as a neurotoxin
Lecture 5, slide 20
Discuss lead as a neurotoxin
Lecture 5, slide 21-24
Give examples of CNS diseases
Lecture 5, slide 25
Give examples of neurodegenerative diseases, their pathology and the proteins that are involved in them.
Lecture 5, slide 27
- Alzheimer’s disease
- Parkinson’s disease
- Prion diseases
What are lysosomal storage diseases? Give examples of lysosomal storage diseases (LSD), their pathology and the major ‘storage’ materials involved
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.
What is CNS inflammation a hallmark of? How is it caused and what does it lead to?
Lecture 5, slide 29
What are the hallmarks of Alzheimer’s Disease (AD) pathology?
Lecture 5, slide 31
Discuss the different hypotheses for AD?
Lecture 5, slide 32-33
How do neurofibrillary tangles form?
Lecture 5, slide 34-35
Give examples of organs affected in disorders of lysosomes and lysosome related organelles (LRO)
Lecture 5, slide 37
What has the studying of disorders of lysosomes and LROs uncovered?
Lecture 5, slide 38-40
What can clinical symptoms of LSDs include?
Lecture 5, slide 41
What are threshold effects in neurodegenerative diseases?
Lecture 5, slide 42
What is excitotoxicity? What is the hypothesis behind it? What can cause it?
Lecture 5, slide 43-45
How can acute excitotoxic shock be treated?
Lecture 5, slide 46
Give examples of diseases potentially involving excitotoxicity
Lecture 5, slide 47
Discuss the specificity of NMDA-induced excitotoxicity.
Lecture 5, slide 51-52
How may diseases lead to neurotoxicity via glutamate?
Lecture 5, slide 53
Give examples of excitotoxins. What do excitotoxins cause?
Lecture 5, slide 54
Give MPTP as an example of a neurotoxin.
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.
Give acrylamide as an example of a neurotoxin
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.
