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Questions and Answers
Which neurodegenerative disease is characterized by protein misfolding and the formation of amyloid plaques that disrupt neuronal communication?
What is the role of chaperone proteins in neurodegenerative diseases?
In the context of neurodegenerative diseases, what does the ubiquitination reaction accomplish?
What impact do neurodegenerative diseases generally have on cognitive and motor functions?
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What is a significant limitation regarding neuronal regeneration in adults with neurodegenerative diseases?
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Which neurodegenerative disease is linked to the degeneration of motor neurons?
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What types of diseases are characterized by the progressive degeneration of neurons in the central nervous system (CNS)?
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Which of the following mechanisms do NOT help reduce the effects of misfolded proteins in neurodegenerative diseases?
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What is the primary reason for the accumulation of misfolded proteins in neurodegenerative diseases?
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Which of the following best describes necrosis?
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What role does intracellular calcium overload play in neuronal death?
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Which substance is primarily associated with excitotoxicity causing damage to neurons?
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What is a major consequence of oxidative stress in neural cells?
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What factor is essential in preventing apoptosis in neurons?
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What is the primary process by which energy is produced in the brain?
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What is the consequence of impaired mitochondrial function within neurons?
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What is the primary contributor to neuronal depolarisation during ischaemia?
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Which of the following is NOT a pathological feature of Alzheimer’s disease?
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Which genetic mutation is associated with an increased risk of developing Alzheimer’s disease?
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What is the primary mechanism by which Memantine operates in the treatment of Alzheimer’s disease?
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Which of the following drugs is NOT approved for the treatment of Alzheimer’s disease?
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What significant cellular outcome follows glutamate acting on NMDA receptors during ischemia?
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What part of the brain is primarily affected by the loss of cholinergic neurons in Alzheimer’s disease?
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Which of the following is a common side effect of Memantine?
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Study Notes
Neurodegenerative Diseases
- Characterized by the progressive degeneration or death of neurons in the CNS
- Result in the loss of cognitive and motor functions
- Can lead to disability and death
- Common examples: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease
- Dead neurons are not replaced in the adult CNS
- Interrupted axons cannot regenerate
- Limited neuronal regeneration makes pharmacological intervention difficult
Protein Misfolding and Aggregation
- Initial step in many neurodegenerative diseases
- Aggregates accumulate with age, forming amyloid deposits
- Amyloid plaques disrupt neuronal communication and trigger inflammatory responses, leading to neurodegeneration
Protective Mechanisms
- Chaperone proteins bind to misfolded proteins and assist in folding them correctly
- Ubiquitination tags defective proteins with ubiquitin, signaling their destruction within the proteasome
Mechanisms of Neuronal Death
- Necrosis: Uncontrolled cell death due to acute injury, infection, or insufficient blood supply
- Excitotoxicity: Glutamate toxicity due to calcium overload, leading to neuronal death
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Apoptosis: Programmed cell death, where cells shrink and are safely removed
- Mitochondrial dysfunction contributes to apoptosis
- Neuronal growth factors (nerve growth factor and brain-derived neurotrophic factor) prevent apoptosis
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Oxidative Stress:
- The brain has high energy needs, requiring ATP production
- Oxygen reduction during ATP production generates reactive oxygen species (ROS)
- Oxidative stress occurs when ROS production exceeds the cell's ability to neutralize them, leading to damage
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Ischemic Brain Damage:
- Interruption of blood supply to the brain initiates neuronal damage
- Depolarization of neurons leads to glutamate release and calcium accumulation
- Nitric oxide production increases
Drugs for Neurodegenerative Diseases
- Cholinesterase inhibitors (Donezepil, Rivastigmine) and Memantine are currently approved for treating Alzheimer's disease
- Memantine is an NMDA receptor antagonist, potentially inhibiting excitotoxicity
- Memantine has a long half-life
- Memantine has a modest cognitive improvement in moderate to severe Alzheimer's disease but is not neuroprotective
- Memantine adverse drug reactions: headache, dizziness, drowsiness, constipation, shortness of breath, and hypertension.
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Description
This quiz covers key concepts related to neurodegenerative diseases, including their characteristics, common examples like Alzheimer's and Parkinson's, and the role of protein misfolding. It also highlights protective mechanisms such as chaperone proteins and ubiquitination involved in neuronal health. Test your understanding of these critical topics in neurology!